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  • Articles  (3,913)
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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Many new Major Histocompatibility Complex (MHC) genes have been discovered in the last 5 years. Defining the polymorphism of these new genes may elucidate their function and their relevance to diseases with MHC associations. Polymerase chain reaction and single stranded conformation polymorphism (PCR SSCP) analyses were used to detect sequence polymorphisms of PERB1 demonstrated by comparing the available genomic sequence of four haplotypes. This study showed that PCR SSCP of PERB 1 is reproducible. In addition, PERB1 alleles segregate within families together with MHC haplotypes. Typing results from the Forth Asia and Oceania Histocompatibility Workshop (4AOHW) cell panel indicate that the identified polymorphisms of PERB 1 are ‘haplotypic’, i.e., unrelated individuals carrying the same MHC ancestral haplotypes carry the same PERB1 SSCP pattern. Interestingly, PERB1 SSCP patterns allow the distinction of ancestral haplotypes which share HLA-B serological specificities, such as HLA-B44 and therefore this analysis can be used to further define MHC haplotypes and thus to improve our understanding of the evolution of this complex.
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  • 2
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Twenty-eight cases of coeliac disease (CD) and seven of dermatitis herpetiformis (DH) have been verified in Iceland. Standard serological techniques were used for HLA typing. Twenty-five individuals with CD were typed, 21 (84%) of whom carried DR3, DQ2. Twelve of these 25 (48%) had DR3, DR7, DQ2, which makes them possibly homozygous for DQ2, and suggests that homozygosity of DQ2 increases the risk for CD. The four DH patients that were typed all had HLA-B8, DR3, DQ2. It is concluded that CD and DH are associated with DR3, DQZ in Icelanders.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: In order to identify new susceptibility markers for Rheumatoid Arthritis (RA), we analysed the dinucleotide repeat polymorphism at the T cell receptor delta locus (TCRD) in 65 RA patients and 99 healthy Belgian controls. A significant under-representation of the A4-A5 TCRD genotype was observed in the RA population.
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: HLA antigens of the Kuwaiti population are not as well characterized as those of other international ethnic groups. We present results for HLA typing of Kuwaiti individuals using commercial Biotest sera. Six hundred and seventy one Kuwaiti were typed for HLA-A, -B, -C antigens and 399 were typed for HLA-DR, -DQ antigens. Antigen frequency and gene frequency were computed for each phenotype observed. The antigens with the highest frequencies were HLA-A2, A1 and A3; B5, B12 and B7; Cw″4 and Cw-l; DR52, DR5, DR3 and DR7; DQ1 and DQ2. HLA haplotypes with strong linkage disequilibrium and characteristic of Kuwaiti population are A2-B5, A1-B8, B7-DR7 and B8-DR3. A comparison study with other populations is presented.
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: HLA-B14 positive haplotypes have increased frequencies in a group of patients with puberty disorders, IgA deficiency and cancer of the ovary. Clinical investigations demonstrated that all these patients have high values of 170H progesteron after the ACTH test which suggests an alterated function of 21 hydroxylase enzyme. In order to investigate whether these B14 positive haplotypes carry the same CYP21 mutation in the various diseases and controls, we have amplified by polymerase chain reaction (PCR) the sections of CYP21B gene which include amino acid positions 172 and 281 where typical mutations are known to occur in 21 hydroxylase deficiency. The presence or absence of the defined mutations was tested by oligonucleotide hybridization using oligonucleotides, labelled with DIG-ddUTP, designed to hybridize with the mutated or with the normal sequence. It was found that regardless of whether the subject tested was a patient or a healthy control the mutation at position 281 was found in all cases carrying HLA-B14, DR1 haplotype. Interestingly, this mutation does not seem to be in association with HLA-B14, DR7 haplotype.These findings suggest that CYP21 gene plays a role in all these differing diseases although it must be stressed that there may be alternative explanations for the observed data.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Patients with CAH, extrahepatic HBV manifestation and healthy children were studied for presence of Gm 1,2,3,10,21 factors and Km 1 factor. Significantly higher frequency of Gm (1, 2, 3, 10, 21) phenotype was shown in CAH group as compared with the other two groups. Relationship between Km factors and examined groups was not found.
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 9
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: HLA-DRB1, DQA1 and DQB1 alleles have been determined in 42 families with one IDDM proband and 64 healthy controls, by oligotyping (PCR-SSO) using primers and probes from the XI International Histocompatibility Workshop. A positive DRB1 *03 and DRB1 *04 association with the disease was observed, whereas DRB 1*11 and DRB 1 *07 showed negative association but 19% of patients carried DRB1 alleles different to DRB 1 *03 or *04. When single alleles were considered, DQA1 *03 showed the strongest association with susceptibility to the disease (RR = 8.2, Pc = 0.00001) but this association was outgrown by 2 and 3 allele combinations, with genotype DRB 1 *04-DQA 1 *03-DQB1*0302/DRB1*03- DQA 1*0501- DQB 1*0201 showing the strongest association (RR = 28, Pc = 0.002). Application of the relative predispositional effect (RPE) method to our data, revealed a further susceptibility risk provided by the DRB1*13-DQA1*0102-DQB 1*0604 haplotype once DR3 and DR4 haplotypes were removed. When DQA1-DQB1 genotypes were analysed for presence of Arg 52 (DQ α) and absence of Asp 57 (DQ β), genotypes SS/SS were found significantly increased in diabetics. Interestingly, one of the strongest associations with the disease was observed with the DQA 1*03-DQB 1*0201 combination encoded mainly by genes in trans (RR = 11.7 Pc = 0.00004). These observations and their comparison with DR-DQ haplotypes in more homogeneous ethnic groups support the stronger influence of the DQ molecule rather than the individual DR or DQ alleles in the susceptibility to IDDM. They also emphasize the need for detailed HLA haplotype studies in non-Caucasian and ethnically mixed populations to gain further insight into the nature of genetic and environmental factors contribution to autoimmunity.
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  • 10
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The human TNF genes are located within the MHC class-III region on chromosome 6. The presence or absence of an Nco-I restriction site in the 5’ non-coding sequence of the TNFβ gene defines two alleles (TNFB*1 and TNFB*2). The segregation of these alleles has been associated with levels of TNFα or TNFβ production in systemic lupus erythematosis (SLE), insulin-dependent diabetes mellitus (IDDM) and in healthy control individuals.Rheumatoid arthritis (RA) is characterized by high levels of TNFα within the synovial fluid and to address the question of whether this could be brought about by a genetic predisposition to high TNF production by RA individuals, we examined the distribution of this Nco-I polymorphism in 98 healthy volunteers and 123 patients with active rheumatoid arthritis. No difference was observed between the normal and RA groups with respect to haplotype segregation or allelic frequency. Furthermore, no difference was observed between DR4+ or DR4- individuals in the control or RA groups.These data demonstrate that the high level of TNFα seen in the joints of RA patients is unlikely to be due to a genetic predisposition of these patients to high TNFα production, as defined by the TNF Nco-I restriction fragment length polymorphism (RFLP).
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  • 11
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 12
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The exceptionally strong independent association found between Lp(a) lipoprotein [Lp(a)] levels and atherosclerotic disorders indicate that Lp(a) is a factor of considerable importance in the pathogenesis of atherosclerosis. The association between Lp(a) and diabetes, rheumatoid arthritis and renal diseases suggest that Lp(a) may be involved in immunological mechanisms.Lp(a) has a great tendency to aggregate and bind to glucosaminoglycans, fibrin and fibronectin and is preferentially retained in the extracellular matrix during development of atherosclerosis and is in vitro phagocytosed by macrophages, probably as small aggregates. It was previously found that the Lp(a) level is significantly related to the HLA class II genotype in male patients with early coronary artery disease. In this paper additional results of interleukin determinations in relation to HLA type and Lp(a) levels are presented and discussed. It is suggested that an autoimmune process, perhaps triggered by a concomitant intracellular infection may occur, especially in patients with inherited high Lp(a) levels in combination with certain inherited HLA class II genotypes.
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  • 13
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: DPB1 locus typing of the 155 cell 4AOHW panel was performed using a PCR-RFLP method. Ambiguity of allele assignment was resolved by amplification using sequence-specific primers. Of the 150 cells for which typings were achieved, three exhibited unusual restriction enzyme fragment patterns, suggesting the possibility of novel DPB1 alleles. Sequence analysis revealed one allele present in the currently reported 46, one novel allele (4AOHW/107) not present among the 46, and one from a non-human primate which is being investigated. Twenty-six (26) of the 34 10IHW cells have been studied previously by cDNA RFLP, and strong haplotypic associations have been demonstrated between DPA1 and DPB1 locus alleles. It is proposed that exploitation of intron polymorphisms marking haplotypes will be an integral part of future DPB 1 typing as a ‘first-pass’ stratification process to minimize the requirement for sequence-based methods to definitively assign DPB 1 alleles.
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  • 14
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: DNA oligotyping was used to determine HLA-A28 subtypes in 25 unrelated Caucasian individuals living in or around Seville, Spain. Results showed that HLA-A*6802 was the most frequent allele, found in 14 individuals (53.8%), followed by HLA-68.3, which was present in eight subjects (30.8%), and both combined represented 84.6% of A28+ individuals in the area. The HLA-A*6801 allele was found in three individuals (11.5%), whereas HLA-A*6901 was present in one subject only (3.8%). Results indicate that the distribution of HLA-A28 alleles can vary among different Caucasoid populations. In this way, the high frequency obtained for A*6802 supports previous studies suggesting that the HLA-A*6802 allele was prevalent in people of the Mediterranean basin, in contrast to A*6801, prevalent in northern European populations.
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  • 15
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 16
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: HLA alleles were studied in Kuwaiti patients with Systemic lupus erythematosus (SLE). Although significant association of B5, B8, and DR3 has been reported in the literature, the most common phenotype for our patients is A3, DR2 as susceptible alleles and DQ1 as a protective gene.
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  • 17
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: A new HLA-B antigen, HLA-B7Qui that appears to be a variant of HLA-B7 has been identified. This antigen, which is HLA-Bw6 associated, reacts with approximately two-thirds of cytotoxic antisera stimulated by HLA-B7 or B27 that lack a B27 or B7 component, respectively. All anti-B7+27 antisera (stimulated by either B7 or B27) react with B7Qui as do most B22-stimulated sera possessing a B7 component. However, sera stimulated by B60, with or without a B7 component, fail to react with B7Qui.Family studies show the B7Qui allele to be unique to the haplotype –HLA-A32 CW6 B7Qui Bf*S C4A*6 C4B*1 DR11 DQ7 (GL02). Six Caucasoid subjects on the panel of 6861 HLA-typed potential bone marrow donors have this antigen (phenotype frequency, 0.08745%; gene frequency, 0.04473%). Work undertaken during the 11th International Histocompatibility Workshop (Reekers et al., 1992) showed that B7Qui has the same isoelectric point as HLA-B702 and HLA-B703 (Bpot) and that B7Qui is distinct from the HLA-B7 variants B703, B7SL, BDT, B7x40, BRI, and B41v.
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  • 18
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: HLA-DRB1*04 allele frequencies have been determined in 184 HLA-DR4-positive unrelated blood donors from the South Wales area, using group-specific polymerase chain reaction (PCR) amplification and hybridization with sequence-specific oligonucleotide probes, PCR amplification with sequence-specific primers, and PCR single-strand conformation polymorphism analysis.Eight of the fifteen known HLA-DR4 sequences were detected in this study. Linkage disequilibrium analysis of HLA-DRB1 *04 and HLA-B, -DR and -DQ alleles revealed distinct haplotypic associations for all the major alleles detected in this population, including the novel linkage of HLA-B55 with DRB1*0407.These results are relevant to the role of HLA-DRB 1*04 haplotypes in determining allogeneic histocompatibility and disease susceptibility.
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  • 19
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 21 (1994), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: A chicken MHC class I (B-F) cDNA from SPAFAS line 11 embryonic liver tissue was isolated and characterized by nucleotide sequencing. Comparing this sequence with previously described B-FcDNAs highlights clustered nucleotide substitutions in exon 3, encoding amino acids located on the a-helical region of the α2 domain.
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  • 20
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Samples from 94 Swedish blood donors were analysed for HLA-DQA1 and -DQB1 alleles by the PCR-SSO technique used in the XIth Histocompatibility Workshop. Seven DQA1 and 12 DQB1 alleles were identified and a total of 17 haplotype combinations were found deduced from the most probable allele combinations. Frequencies calculated from these haplotypes were compared to those calculated from the phenotypes according to Mattiuz et al. (1970). There was no significant difference in the frequencies of the 17 haplotype combinations deduced. Eight haplotype combinations had exactly the same frequencies and four had approximately the same frequencies independent of the calculation method used. The DQA1*0301-DQB 1*0302, DQA1*0501-DQB1*0201, DQA1* 0101-DQB1* 0501, and DQA1*0102-DQB1*0602 were the most frequent haplotypes with frequencies over 0.130.
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  • 21
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 22
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We have studied the genotypic, haplotypic, and allelic distribution of germline Restriction Fragment Length Polymorphism (RFLP) of T-cell receptor (Tcr) α, γ, and δ loci in 75 insulin-dependent diabetes mellitus (IDDM) patients and 84 healthy blood donors as control population. The restriction endonuclease PvuII produces three allelic fragments of Tcr C-γ (TcrCG) gene segment of 16,13, and 11.3 Kb respectively. Our observations revealed that PvuII/TcrCG RFLP allelic distributions were not significantly different in the IDDM and the control group. However, 85% of IDDM patients carried HLA DR3 and/or DR4 haplotypes, and when comparing these patients with a second group of HLA DR3+ and/or DR4+ healthy individuals, the 11Kb/PvuII fragment of TcrCG gene was found to be associated with IDDM patients (χ= 11.4, P= 0.003). 54.9% of IDDM patients carried at least one 11.3 Kb allele vs. 21% in controls (χ= 10.77, P = 0.004). No significant association was found between RFLP in Tcr, Cα, Cδ, Vγ9 loci and IDDM.
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  • 23
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The outcome of subcutaneous infection with L. major NIH 173 was evaluated in a series of recombinant inbred and congenic strains, as well as F2 progeny generated from a genetic linkage testing stock carrying the visible markers Ra, Os, and Pt. The disease parameters monitored were the incidence of open or necrotic lesions and footpad depths of infected feet, and the incidence and number of amastigotes in livers following infection. Regions of mouse chromosomes 2, 4, 7, 8, 12 and 15 were excluded from linkage to a gene (Scl-1)involved in the susceptibility of inbred strains of mice to cutaneous infection with L. major NIH 173 by F2 and congenic strain analyses. Strain distribution patterns generated for Scl-1 in the CXB and CXS recombinant inbred strains suggested linkage to the distal end of mouse Chromosome 11.
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  • 24
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Natural killer cell (NK) activity is regulated by both the H-2 and non-H-2 genes. Using bilineal congenic HW26C and HW13 mice which differ from the background strain C57BL/6By (B6) in a region of chromosome 4, we investigated the role played by a gene/genes in a segment of chromosome 4 of BALB/cBy on NK cell activity. Percoll separated low density spleen cells from young HW26C and HW13 mice showed a 3.5 fold higher NK activity than the B6. We also observed that the increase in NK activity of HW26C was not due to an increase in the number of NK cells. Using five other bilineal congenics containing different regions of chromosome 4 of BALB/cBy, we observed that the putative gene(s) regulating NK activity may be located between b and IFN-α/β genes of chromosome 4. The level of NK activity of (B6xHW26C)F1 ranked between the HW26C and B6 suggesting that the gene product described is inherited in an incompletely dominant fashion.
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  • 25
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We describe a new, non-radioactive microtitre plate assay for the analysis of genetic variations at the DNA level. The new method combines hybridization of oligonucleotides with PCR amplified DNA in liquid phase with detection in solid phase using an elisa-reader. Genomic DNA is labelled with digoxigenin during PCR using a nucleotide mix containing DIG-11-2′-deoxy-uridine-5′-triphosphate (DIG-11-dUTP) DIG labelled, amplified genomic DNA is hybridized in solution with an oligon de which is labelled with one biotin at its 3′-end, using biotin-16,2′,3′-dideoxy ine-5′-triphosphate (BIO-16-ddUTP) and DNA deoxynucleotidylexo-transferase (TdT). The hybridized complex is immobilized in a streptavidin (SA) coated microtitre plate via the biotin and detection of digoxigenin is performed using anti-digoxigenin horseradish peroxidase, fab fragments (anti-DIG-POD), and the colorimetric substrate 2,2′-Azino-di-(3-ethylbenzthiazolinsulfonat[6]) (ABTS®). The resulting absorbtion of the assay is analysed in a microtitre plate reader. This method results in highly specific and sensitive hybridization signals and with the 15 oligonucleotides chosen, allows the typing of DR1-DR10.
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  • 26
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: In this note is recommended a unified nomenclature for allotypes and variants of human complement factor B, which was approved by the Nomenclature Committee of the International Union of Immunological Societies (IUIS).
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  • 27
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    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: By quantitation of elutable immunoglobulin G in a recently described elisa, the number of HLA class I and II molecules on B-cell lines was determined using monomorphic monoclonal antibodies. An average number of 183 000 binding sites per cell for HLA class I-, 99000 for HLA-DR-, 63000 for DQ- and 42000 for DP-specific monoclonal antibodies were determined. The small amount of HLA class II molecules can in part explain the difficulties observed in HLA class II typing or in detection of class II antibodies using the lymphocytotoxicity text.
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  • 28
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    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The second exon of the DRB1 gene encoding for the first domain of the HLA-DR β-chain was sequenced in 16 patients (10 DR4/DR1 positive, 6 DR4/DR1 negative) with seropositive rheumatoid arthritis (RA). We could confirm the strong association of susceptibility to RA with functionally equivalent conformations on otherwise distinct MHC molecules. At least one HLA-DR allele in all of the analysed DR4 or DR1 positive patients showed such an epitope with a minimal variability limited to residue 71.However, in HLA-DR4 and -DR1 negative patients such a similar epitope could not be detected.
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  • 29
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    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: In order to produce mAbs directed specifically against HLA-DR10 molecule, transfected mouse L cells, expressing the DRB 1*1001 allele, were used to immunize C3H mice over a period of 4 weeks. Two mAbs, 2C12 and 4B6, derived from this fusion were found to recognize, with different affinity, polymorphic epitopes of DR10 that are shared with DR1, 3, 7, and 9. These mAbs were screened on a large panel of homozygous B lymphoblastoid cell lines using microlymphocytotoxicity and the results were confirmed by flow cytometry. The reactive pattern of 2C12 and 4B6 was compared to that of MP10 human mAb also recognizing the DR10 specificity in addition to DR1, 2 and 9.Based on serologic specificity and cellular absorption experiments, we conclude that the epitopes the murine and human mAbs respectively recognize on the DR10 molecule, are probably different.
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  • 30
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    International journal of immunogenetics 20 (1993), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Deficiency of complement component C4 is considered playing a role in the genetic predisposition for systemic lupus erythematosus (SLE). The purpose of this study was to characterize the genomic alterations of the C4 and CYP21 genes in 40 caucasoid patients with SLE by C4 allotyping and by RFLP analysis. Nineteen patients (47.5%) carried C4A null alleles and eight patients (20.0%) C4B null alleles. SLE patients had more frequent C4A null alleles (47.5%) than healthy individuals (20%) (X2= 10.75; P 〈 0.005). The commonest molecular alteration in the patients with C4A null alleles was a large gene deletion affecting both C4A and CYP21A genes. However, among the patients with C4A null alleles, 16.7% persons had no detectable C4A deletion. The non-expression of C4A gene might be due to defects at various levels of gene expression (i.e. transcription and translation).Among the patients with C4B null alleles, 62.5% persons had no detectable gene lesion, whereas 37.5% showed a C4B deletion including both C4B/CYP21A or C4B/CYP21B genes.Duplication of the C4B gene was not rare in SLE patients, as we found 15.0% of the patients with a heterozygous C4B/CY21A gene duplication. The patients typed as having C4B gene homoduplication (B1,1) demonstrated two long C4B loci, whereas heteroduplication (B1,2) displayed two short loci, therefore the type of C4B gene duplication may be related to the gene length.In conclusion, C4 deficiencies observed in 26 of the 40 SLE patients studied were very heterogeneous. In every case, the gene alteration affected both C4 and CYP21 genes.
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  • 31
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    Notes: A novel non-radioactive protocol for molecular generic HLA-DR typing is introduced, employing sequence specific oligonucleotides (SSOs) enzymatically 3′-labelled with biotin-14-dATP via terminal deoxynucleotidyltransferase in a tetramethylammonium chloride hybridization procedure. The detection reaction is carried out, using streptavidine conjugated horseradish peroxidase which is bound to the SSOs, in combination with a light emitting detection system. Fourteen SSOs and one control SSO are employed for generic HLA-DR typing in a one-step protocol. In order to demonstrate the suitability of this procedure, 5 homozygous typing cell lines and samples of 11 pretyped individuals which include most serologically defined HLA-DR specificities (DR1, 2, 3, 4, 11, 12, 6, 7, 8, 9,10, 52, and DR53) are analysed with the panel of 14 SSOs. The typing results show that this protocol, which avoids the use of radioisotopes, combines high specificity and easy handling. It also allows typing of poorly amplified samples because even after longer exposition times no false positive signals were observed and is particularly suitable for routine molecular HLA-DR typing on the generic level. In addition it can easily be adapted to DP and DQ typing or DR subtyping.
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  • 32
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    International journal of immunogenetics 19 (1992), S. 0 
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    Topics: Biology , Medicine
    Notes: The aim of the study was to determine whether C5 deficiency in the mouse is associated with resistance to the development of secondary amyloidosis. Chronic inflammation was induced in the F2 progeny, derived from matings between amyloid-susceptible and amyloid-resistance mice, by daily injections of azocasein for thirty days. Using a restriction fragment length polymorphism generated by digestion of genomic DNA with the restriction enzyme HindIII, C5 sufficient and deficient DNA can be clearly differentiated. Eight mice were found to be C5 sufficient, 32 were heterozygotes and 14 were found to be C5 deficient. Grading of the splenic amyloid load from negative to 4+ was performed after staining tissue squashes with Congo red and viewing them under a polarizing microscope. Seventeen mice were noted to have negative to trace, 18 had moderate (1+-2+) and 19 had heavy (3 H+-4+) amyloid deposition. There was no correlation between splenic amyloid load and C5 deficiency. Based on these results it is clear that C5 deficiency and resistance to secondary amyloidosis are not associated.
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  • 33
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    International journal of immunogenetics 19 (1992), S. 0 
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  • 34
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    International journal of immunogenetics 19 (1992), S. 0 
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    Notes: The relative distributions of 12 HLA-DR6-related HLA-DRB1 alleles in indigenous populations of Australia, Melanesia, Polynesia, Micronesia, and northern and southern China have been determined by analysis of nucleotide sequence polymorphisms in 364 examples of HLA-DR6 positive chromosomes. Oligonucleotide hybridizations of polymerase chain reaction products of HLA-DQA1, DQB1, DRB1 and DRB3 genes generated 24 HLA-DR6-related haplotypes. The study aimed to determine the regional distribution of DR DQ haplotypes associated with three novel HLA-DR6 alleles, namely DRB1*1408, 1409, and 1410, known to occur in Australian Aborigines, to gain further insights into the molecular phylogeny of these alleles. DRB1*1408 was the most common HLA-DR6 subtype in Oceania, although it was not detected in Chinese. In Australian Aborigines and Papua New Guinean highlanders, DRB1*1408 was associated with DRB3*0202, while in Polynesians and Micronesians it was associated with DRB3*0101. The different haplotype arrangements, together with the near absence of DRB1*1408 in coastal Melanesians, suggest the possibility that two independent mutations have generated DRB1*1408 in Australia and Oceania. DRB1*1409 and 1410 alleles were confined to Australian Aborigines, while DRB1*1407 was found exclusively in Melanesians; DRB1*1401 was the only HLA-DR6 allele represented in all study populations. The population-specific HLA-DR6 alleles and haplotypes have important implications for unrelated bonemarrow donor registries in Australia and Oceania.
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  • 35
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    Notes: The human gastric cancer cell line MKN 45 was derived from the tumour of a blood group A individual, and was known to express large quantities of blood group A-antigen. Using immunofluorescence we found the MKN 45 cells, donated from the Japanese Cancer Research Resources Bank, consisted of A-antigen positive cells (18%) and A-antigen negative cells (82%). After limiting dilution, wild type and mutant cells were cloned with regard to the expression of a cell surface A-antigen. ELISA was used to detect A-antigen in the cell extract of the wild type cells, but none was evident in those of the mutant cells. However, blood group A-gene-specified transferase activity of the mutant cells was comparable to that of the wild type cells.
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  • 36
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    Notes: We analysed alloreactive T-cell clones selected for their differential recognition of DR variants differing in the third hypervariable region (hvr) of the DRB1 gene (amino acid positions 67–70–71). This polymorphism leads to two main hvr3 types: a basic form (Leu67-Gln70-Arg/Lys71) and an acidic form (Ile67-Asp70-Glu71) where residue 70 is probably directly accessible to the TCR on DRβ chains. The TCRs have been sequenced. Three DRw13-reactive clones use similar Va2 and Vβ13 gene family members but differ mainly by their cross-reactivity towards acidic or basic DR4 variants and by the sequence of CDR3 on their TCRα and/or β chains. One anti-DRw13 clone cross-reacts with most specificities sharing the DRw13 type of hvr3 and reciprocally one anti-DRBon (DRB1*0103) clone cross-reacts with DRwl3. These two clones use similar V0 genes and share negative charges in CDR2α at position 56. They also share these negative charges in CDR2α with two other clones reacting specifically with DRBon, the acidic variant of DR1. We hypothesized that the selective recognition of positively or negatively charged residues on the DR(3 chain would necessitate reciprocal charges on the TCR complementarity determining regions (CDRs) responsible for this interaction. This facilitated identification of those residues of the TCR that possibly interact with the hvr3 determinant of HLA-DR. From these observations the mechanisms allowing the recognition of alloantigens by these T-cell clones are discussed.
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  • 37
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    Notes: We describe a rapid non-radioactive DNA typing of the serological types DR1-DRw10 using polymerase chain reaction (PCR)-amplified DNA and 15 sequence-specific oligonucleotides (SSO) which are labelled enzymatically at their 3’end with one digoxigenin (DIG). The hybridized SSOs were detected using anti-DIG alkaline phosphatase and Fab fragments and visualization was obtained with the chemilumine-scent substate 3-(2‘-spiroadamantan)-4-(3′-phosphoryloxy)-phenyl-1,2-dioxetan (AMPPD). The results were identical with those of the previously used 5-bromo-4-chloro-3-indolyl-phosphate (BCIP)/4-nitrobluetetrazolium chloride (NBT) system. The use of AMPPD is more rapid and allows the repeated rehybridization of the membrane-bound DNA.
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  • 38
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    International journal of immunogenetics 18 (1991), S. 0 
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    Notes: Cell lines and a clone established from the C57BL/6 (H-2b) Lewis lung (3LL) tumour were previously characterized with respect to tumour growth and metastatic spread in vivo, and to the expression of a 3LL tumour-specific antigen (3LL TA) using a monoclonal antibody raised in syngeneic mice immunized with 3LL cells. No correlation was observed between the presence of 3LL TA and the prevention of metastatic spread which suggests that the immune recognition of this tumour antigen requires the presence of a self H-2 molecule absent from these tumour cells. Indeed, radioimmunoassay (RIA) and cytofluorometric analysis using specific monoclonal antibodies have shown that the H-2Kb molecule was not expressed at the cell surface of all 3LL cell lines and clones, while the H-2Db molecule was present at normal levels. This defect, which was not the consequence of a lack Of (32m expression, was accompanied by an absence or a marked reduction of the H-2K mRNA level (which has been reversed in the M4 cell line by in vitro gamma interferon treatment), while the H-2D class I gene was normally transcribed. Another defective transcription was also observed for a gene in the Tla region (gene 37). This low‘37’phenotype was corrected by in vitro treatment of the M4 cell line with gamma interferon, which indicates that this class I gene of the Qa/Tla region has an interferon response sequence in the promoter.
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  • 39
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    International journal of immunogenetics 18 (1991), S. 0 
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    Topics: Biology , Medicine
    Notes: Using H-2 recombinant congenic strains of mice, genetic analysis of resistance to murine hepatitis virus type 3 (MHV3)-induced paralysis was performed. It appeared that both H-2K and H-2D, two class I gene regions of the mouse major histocompatibility complex (MHC), can play independent significant roles in the establishment of such resistance.
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  • 40
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  • 41
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    International journal of immunogenetics 18 (1991), S. 0 
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    Topics: Biology , Medicine
    Notes: The HLA-DQw2 specificity, homogeneous in serology, is strongly associated to two HLA-DR specificities: DR3 and DR7. These alleles are found mainly on DQw2 bearing extended haplotypes with strong linkage disequilibrium. We describe, with BamHI, HindIII and RsaI, two restriction fragments length polymorphisms (RFLP) for the A gene of DQw2. These two subtypes correlated with the DR3 and DR7 specificities. Interestingly, by non-equilibrium pH gradient electrophoresis (NEPHGE), two DQα chains were also found, respectively correlated with the same DR specificities. In addition, Hindi polymorphism allowed us to distinguish several patterns of B genes for (DR7) DQw2 haplotypes but without any detectable association with another HLA marker. However, only one DQ(3 chain was found by NEPHGE in the (DR7) DQw2 haplotype. Furthermore, MncII discriminated the B genes of the two extended haplotypes: (B8, DR3) DQw2 and (B18, DR3) DQw2. The same result was found by NEPHGE: two DQβ chains were described, corresponding to the same extended haplotypes. The use of exon-specific DQB probes showed that the genomic polymorphism in DOw2 haplotypes is located, at least, at the 3’end of the gene. These data add new characteristics to the different DQw2 extended haplotypes.
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  • 42
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    International journal of immunogenetics 18 (1991), S. 0 
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    Notes: Differences between the mouse Ly5a and Ly5b alleles can be distinguished on the basis of polymerase chain reaction (PCR)-restriction enzyme analysis and differential monoclonal antibody reactivities. To more precisely map the Ly5 gene on the mouse chromosome 1, analytical DNA and protein tests were performed on recombinant inbred strains of mice prepared from SJL/J (Ly5a) and B ALB/cke (Ly5b) progenitor strains. Each recombinant inbred strain was characterized to determine whether it carried the Ly5a or Ly5b allele. Both assays, DNA-PCR and protein-immunofluorescence, yielded identical results for each strain examined. Placement of the Ly5 gene with respect to other characterized markers of mouse chromosome 1 for these recombinant inbred mouse strains shows a gene order of Idh-1.Ity:Pep3:/Ly5, CfhJ.
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  • 43
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    International journal of immunogenetics 18 (1991), S. 0 
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    Notes: Polymerase chain reaction/oligonucleotide typing was used to identify HLA-Cw*0601 (Cw6) in patients with psoriasis and psoriatic arthritis. The assignment of HLA-Cw*0601 was established by the concordant presence of codons for alanine (position 73), lysine (position 80) and tryptophan (position 97). The frequencies of all three codons were increased in the patient groups.
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  • 44
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    International journal of immunogenetics 18 (1991), S. 0 
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  • 45
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: The in vitro proliferative response of T cells primed with human thyroglobulin (Tg) was compared in 11 independent haplotypes on B10 background. B10.K and B10.S mice were the most responsive, whereas, with the exception of B10.PL (H-2u, all other B10 congenics were intermediate responders. The two best responders to in vitro challenge with human Tg, of the k and s haplotype, are the same as those showing H-2-linked susceptibility to induction of experimental autoimmune thyroiditis (EAT) with mouse Tg. Since shared epitopes on human and mouse Tgs have been shown to be thyroiditogenic by adoptive transfer studies in CBA (H-2k) mice, the findings indicate that shared epitopes may be studied in appropriate (i.e. EAT-susceptible) strains of mice. Therefore, we proceeded to develop methods to produce T-cell lines and hybridomas to human Tg in B10.K and B10.S mice, test their cross-reactivity to heterologous Tgs and their Ia restriction patterns. By using antigen-presenting cells from recombinant strains, we identified restriction elements encoded by the I-A subregion alone and a combinatorial molecule from the I-AI/I-E subregions.
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  • 46
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: Intracytoplasmic μ-positive pre-B cells (μ+VH315− cells) transformed with Abelson virus continuously produced cells (μ+VH315+ cells) that were double-stained by anti-μ and anti-VH315 antibodies which specifically recognized the immunoglobulin heavy chain variable region identical or closely related to that of MOPC315 myeloma protein. Southern blot analysis indicated that the μ+VH315+ cells were generated from the μ+VH315- cells by the VH315·D·JH2 to a germline JH3 joining on the non-productive VH315·D·JH2 allele, which resulted in the production of μ-chains with variable region detectable by anti-VH315 antibodies. Therefore, it is strongly indicated that VHDJH to JH joining is not blocked in μ-chain-producing pre-B cells, and thus is free from allelic exclusion machinery.
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  • 47
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    International journal of immunogenetics 17 (1990), S. 0 
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  • 48
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: Forty-six numbered Rh antigens which are detected in serological tests are extant; antigens which were most recently numbered are of high or of low incidence. The identification of high incidence Rh antigens through studies involving cells with rare Rh phenotypes, including Rhnull cells, is described briefly. The serological investigations and family studies required to show that a low incidence antigen is an Rh antigen are illustrated by a description of the JAL (Rh48) antigen. Heterogeneity of polymorphic Rh antigens revealed by using monoclonal antibodies (MABS) is demonstrated by consideration of the Rh antigen D. A summary of results of serological tests shows that monoclonal anti-D antibodies define eight D epitopes. Partial D antigens of the D categories are reassessed in terms of expression of D epitopes.
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  • 49
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    International journal of immunogenetics 17 (1990), S. 0 
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  • 50
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: Eleven monoclonal anti-IgG antibodies were evaluated by ten laboratories for possible AHG reagent use by the ISBT/ICSH protocol. Three of the anti-IgGs were selected by tests with weak Fya sensitized cells as this represents the best screening test. One of the IgM class anti-IgGs (205) equalled ISBT/ICSH reference reagents (R3P and RIIIM) against weak anti-D, -K and Fya sensitized cells and it reacted with all four subclasses of IgG. Thus, subject to satisfactory stability and extended trials with a wide range of weak antibodies, monoclonal anti-IgGs for AHG reagent use are now a possible alternative to conventional rabbit anti-IgG.
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  • 51
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: We have biochemically characterized by 2D (two-dimensional) electrophoresis three novel class I molecules called A166, A149 and A216 expressed by 1591, a UV-induced fibrosarcoma, and have compared them to class I molecules expressed by mice of the H-2q and H-2s haplotypes. A166 and A149 are very similar if not identical to Dq and Lq respectively. We have shown, using HPLC (high-pressure liquid chromatography) tryptic peptide mapping, that the expression of A166 is approximately three fold greater than A149, reminiscent of Dd compared to Ld. In addition A216 possess an identical isoelectric point to that of the Ks molecule. We demonstrate that outbred Swiss Webster mice express an analogous constellation of class I molecules and we conclude that our results can be most easily interpreted in terms of an allogeneic origin for the novel class I molecules expressed on 1591.
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  • 52
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: Immunoisoelectrofocusing (IIEF) reveals a microheterogeneity of human serum IgA controlled by an autosomal polymorphic gene, termed S. The microheterogeneity disappears when sialic acid is removed from serum glycoproteins by neuraminidase treatment. It can be postulated, therefore, that S encodes a sialyltransferase which attaches sialic acid at the outer prosthetic chains of IgA.
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  • 53
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    Notes: Insulin-dependent diabetes mellitus (IDDM) is associated with several DR3- or DR4-containing ancestral haplotypes (AHs). Using pulsed field gel electrophoresis (PFGE), long range maps of 35 haplotypes have been derived and classified. Two diabetogenic DR3-containing AHs (8.1 and 18.2) possess deletions in the central non-HLA region; these have not been found on non-diabetogenic AHs tested to date. In addition, 8.1 and 18.2 also carry other deletions not found on other AHs. Three DR4 containing AH lack a Not 1 site, which may imply excision of an unidentified gene. These and other data suggest that deletions may be relevant to the pathogenesis of autoimmune disease, possibly through causing quantitative differences in autoimmune responses involved in IDDM. The MHC contains several regions of potential interest in relation to susceptibility to IDDM; these may explain the association with only certain DR3- and DR4-carrying AH and DR3,4 heterozygosity in terms of cis and trans interactions. On the other hand, the class I1 region may be particularly important in protection.
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  • 54
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: A. Read: Medical Genetics: An Illustrated Outline.
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  • 55
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: MHC class II molecules and self antigens, such as Mls, influence T-cell selection by clonal deletion of potentially self-reactive T cells. In order to examine the role of various class II molecules in the T-cell receptor-self antigen interaction, class II transgenic and recombinant mice were analysed for TCR expression. Our studies indicate that the Aα and Eα chains can present Mls gene products for the clonal deletion of Vβ6-bearing T cells, and that the Aαq chain is defective in this process. We have also shown that Eα Aβ heterodimer in transgenic and recombinant mice is expressed and functions to delete I-E reactive Vβ11 T cells, demonstrating again the role of the Eα molecule.
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  • 56
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    International journal of immunogenetics 17 (1990), S. 0 
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  • 57
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    Notes: We assessed HLA-DR types and investigated serum samples for islet-cell cytoplasmic antibodies (ICA) in 31 Danish patients with chronic pancreatitis. The antigen frequencies were compared with those in 1177 unrelated healthy Danish controls. Twenty patients had insulin-dependent diabetes and 11 had normal intravenous glucose tolerance. No significant differences in the frequencies of DR3, DR4, or DR2 were found between patients with insulin-dependent diabetes and patients with normal glucose tolerance or between any of these groups and controls. ICA were negative in all patients with chronic pancreatitis. It is concluded that the beta-cell dysfunction in insulin-dependent diabetes in chronic pancreatitis differs from that of classical insulin-dependent diabetes.
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  • 58
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: The ACI or BDIV rats responded with decreased or increased neutrophil levels in blood after the N-methyl-N-nitrosourea (MNU) administration. The F1 hybrids had decreased neutrophil counts, and the BDIV × (BDIV × AC1)Fl backcross offspring showed two phenotypes. The sex of the rats and the neutrophil response to MNU assorted independently. The results indicated that the neutrophil response to MNU was regulated by autosomal gene Nrm-1 with two alleles. The Nrm-Id regulates the decrease and the Nrm-1i regulates the increase of neutrophils in blood after the MNU administration. The results were confirmed by the SKUMIX computer program.We found that the Nrm-1 gene was linked to the agouti locus (chi-square = 10–3, P 〈 0.001). The map distance between two genes was 33 ± 5 cM. The Nrm-1 gene thus resides on the linkage group IV of the rat.
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  • 59
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: A comparison of lymphocyte antigens showed that 32 of the 33 BoLA antigens defined at the third international BoLA workshop (Bull et al., 1989) corresponded to previously defined local antigens (Stear et al., 1988). The third workshop antigen w18 had no locally defined equivalent. All 32 antigens were shown in family studies to be expressed by autosomal co-dominant genes, and all 32 workshop antigens were shown to be products of the BoLA system. After excluding the supertypic antigens, nearly all animals tested possessed only one or two antigens and there were no observed recombinants in family studies. These results do not exclude the possibility that the 32 workshop antigens are the products of one locus (BoLA-A).
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    Notes: The CCGG and GCGC sites of the human HLA-DRα gene are hypermethylated in human tissues (including B-lymphocytes, T-lymphocytes, muscle, brain, sperm, skin, kidney, suprarenal and mammary glands) and three B-lymphoid cell lines. Therefore, the HLA-DRα gene can be transcribed even though extensively methylated. The only exception to the hypermethylated state of the HLA-DRα gene is represented by one or both of the two HhaI sites (H1 and H2) localized in the 5’portion of the gene. Analysis of the computer-generated secondary structure of the HLA-DRα mRNA suggests that the H1 and H2 sites belong to a region (5′-GAGCGCCCA-3′/5′-UGAGCGCUC-3′) exhibiting extensive base pairing. Therefore, unmethylation of these CG sites can contribute in preventing mCG→TG/CA changes in this region, which would lead to extensive alterations of the secondary structure of the 5’portion of the HLA-DRα MRNA.On the other hand, the selective pressure to maintain unaltered the methylated CG dinucleotides in the coding regions of the HLA-DRα gene could be due to codon restrictions, since the majority of the methylation-related CG→TG or CG→CA variations would generate aminoacid changes.Accordingly, the analysis of different HLA-DRα genomic sequences indicates that variations of the CpG dinucleotides occur only in the non-coding portions of the HLA-DRα gene.
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: Several reports have shown that HLA-B8,DR3 positive subjects may display some changes in immune parameters when compared with HLA-B8,DR3 negative ones and are prone to develop several immunological diseases. In the present study we have analysed the proliferative response to phytohaemagglutin (PHA) in HLA-typed healthy subjects. A twin method was also employed to assess the role of genetic and environmental factors in the regulation of the response to the mitogen. It was not possible to demonstrate any difference in proliferative response to optimal doses of PHA between groups of subjects carrying or not carrying the HLA-B8,DR3 phenotype. When suboptimal responses were studied, however, the results showed that ly-mphocyte responses were significantly decreased in HLA-B8,DR3 positive subjects compared with the negative ones. Moreover, the experiments performed with twins demonstrated that environmental factors were more important than genetic factors in the proliferative response to mitogen. The fact that the HLA-B8,DR3 phenotype affects the suboptimal response to PHA although environmental factors are more important than genetic factors in the response to the mitogen seems of some interest. However, these results could be consistent with the high incidence of autoimmune disorders among HLA-B8,DR3 positive individuals.
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  • 62
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    International journal of immunogenetics 17 (1990), S. 0 
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    Notes: Cell surface expression of class II major histocompatibility complex encoded (la) molecules depends on association of the component α and β chain into a stable heterodimer. Studies on cell lines transfected with MHC class II genes have revealed important limitations on the assembly of haplotype-mismatched Aα:Aβ complex. In order to study α: β chain pairing restrictions in vivo a number of lines of transgenic mice carrying the Aαk gene were generated. The transgene was studied in the context of H-2b, H-2s, H-24, H-2u, H-2f and H-2v haplotypes. Initial FACS analysis of spleen and peripheral blood cells showed no Aαk expression. Spleen cells stimulated with LPS and analysed by FACS showed Aαk expression in three different H-2b strains as well as H-2u, but not in others. These data indicate that Aαk can associate with Aβb and Aαk, but not with Aβs,Aβq, Aβf, Aβv.
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: The localization of TNF genes on the short arm of chromosome 6 between HLA B and the complement genes focused attention to that genetic region which harbours many immunologically relevant genes and is also thought to hold susceptibility genes for a variety of autoimmune diseases that are linked to specific alleles of particular loci in the HLA D region. Since the recently established HLA-DR-DQ variation accounts only for part of the genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) we searched for genomic variation of the tumour necrosis factor (TNF) alpha. We have identified a TNF-alpha restriction fragment length polymorphism (RFLP) with N coI and analysed diabetic patients including their families, controls and homozygous typing cell lines (HTC) defined by the 10th International Histocompatibility Workshop. Segregation analysis in families and HTC results show a strong linkage of the TNF-alpha 5.5 kb allele with DR types in particular with AIB8DR3. This tight linkage of TNF-alpha alleles with extended haplotypes and the significant increase of heterozygotes in patients could lead to some explanation of the DR3 association with a variety of autoimmune diseases particularly IDDM.
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  • 64
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: The role of the MHC class II antigens in the activation of resting human B lymphocytes (B-Go) was examined with respect to both early and late events in the activation process.The (Ca2+)i induced by anti-IgM was enhanced in the presence of, or following pre-incubation with, an anti-MHC class II DR antibody (D1.12). Pre-incubation with a sepharose conjugated antibody (Seph.-D1.12) augmented the proliferation of B-Go in response to a sub-optimal concentration of anti-IgM.The 2D PAGE profile of B-Go differed from that of in vivo activated B lymphocytes. The 2D PAGE profile of B-Go activated by Seph.-D1.12 was not identical to the profile of B-Go activated by either anti-IgM or PMA.These data suggest that the activation of B-Go via the class II antigens shares part of the pathway of anti-IgM induced activation but does not follow an identical pathway.
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  • 65
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: We established the organization of the AKR Qa region and determined the sequence of the 44 and Q5 genes. Restriction mapping and genomic Southern blot analysis revealed that the AKR strain codes for only three H-2K homologous genes in this region. The AKR Q5 gene is not homologous to the Q5 gene of the C57BL strain, but is presumably allelic to the Q5 gene isolated from Balb/c. The organization and structure of the AKR Qa family is virtually identical to the Qa genes of the C3H mouse. The AKR Q5 gene, in contrast to other H-2K homologous Qa region genes, codes for a typical transmembrane region, and upon transfection into BHK cells, a 1.6 kb Q5 transcript is detected.
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  • 66
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: The metastatic B16 mouse melanoma shows a low cell surface expression of H-2Kb and H-2Db class I antigens on cells of both the high-metastatic line B16-F10 and the low-metastatic line B16-F1. Similarly, newly generated clones of these lines, having different metastatic properties, all express low levels of major histo-compatibility antigens. One of these clones, the high-metastatic F10.9, was transfected with H-2Kb genes to generate H-2Kb-expressing transfectants. The resulting clones showed reduced tumourigenicity and a low metastatic phenotype. Unlike the parental cells, H-2Kb-positive transfectants are potent inducers and sensitive targets of H-2Kb-restricted syngeneic cytotoxic T cells. Immunization of mice with H-2Kb-positive transfectants conferred protection against a subsequent challenge with Kb-positive transfectants but had only a small effect on growth and metastatic spread of parental cells.
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: In this report we demonstrate that lowered expression of the H-2 antigens on RadLV-induced tumour cells is a result of depressed levels of stable mRNA in these cells. Whether this observation is a result of lowered transcription or of mRNA instability is under investigation. In an effort to determine which viral sequences are essential for mediating both the H-2 regulatory function and the transforming function of RadLV, we have begun to assemble newly integrated proviral genomes from tumours. The restriction enzyme cleavage sites of four isolates are presented; these isolates differ substantially from RadLV genomes previously presented. One of these molecular clones is shown to encode a non-defective B-tropic, ecotropic virus which when reinjected into resistant mouse strains can mediate the up-regulation of H-2Dd antigen expression. Finally, possible mechanisms of H-2 regulation are discussed.
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    Notes: Expression of beta human chorionic gonadotropin (βhCG) by bladder tumours has been shown to be associated with increased metastases and resistance to treatment with radiotherapy and chemotherapy. Preliminary results from typing frozen tumours using monoclonal antibodies against HLA determinants show reduced or lost expression of one or more antigens in two thirds of patients studied with a trend for more malignant behaviour and inability to generate tumour infiltrating lymphocyte expression using Interleukin-2 in those patients whose tumours demonstrate loss. In this series βhCG expression was only seen in a subgroup of those demonstrating loss of HLA antigen expression. Studies of βhCG secreting bladder cancer cell lines showed that it was possible to induce class II HLA antigen expression with gamma Interferon, and that this treatment but not alpha Interferon reduced βhCG production by the cell line.
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    International journal of immunogenetics 16 (1989), S. 0 
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: mAb KUL/05, a novel murine monoclonal antibody, reacts with molecules displaying the typical tissue distribution and molecular profile of class II MHC antigens. An extensive scrutiny employing serological and immunochemical assays on DR homozygous and DRα- mutant cell lines has shown that this reagent displays some additional, interesting features, namely mAb KUL/05 (a) binds in a broadly monomorphic fashion to cells of DR1 through seven specifities, (b) recognizes a determinant shared by a large proportion of DR, DQ and DPβ chains from most haplotypes, in both their monomeric and α chain-associated forms, and (c) reacts with frozen, acetone-fixed, as well as conventional, formalin-fixed, paraffin embedded tissues. Thus, mAb KUL/05 is likely to represent a useful adjunct for the study of the expression of class II MHC products in normal and pathological tissue specimens.
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: Substrains of NZB mice have been compared by Southern blot analysis using several probes. The restriction fragment length polymorphism of probes derived from the Igh-V, Igk-V, Tcrα-C loci and of the long terminal repeat of the mouse mammary tumour virus revealed that NZB/BlLwPtIbm were grossly different from NZB/BlNJ and NZB/BlOla. Comparison with mouse strains of the Igk-V haplotypes a and d suggested that NZB/BiLwPtIbm contain genetic material of the C58 mouse strain.
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: Kaposi's sarcoma is associated with an increased frequency of HLA-DR5. The hypothesized model of a susceptibility gene in linkage disequilibrium with DR5 may be tested by haplotype analysis in familial Kaposi's sarcoma. Our finding of no common haplotype among afflicted members of a family provides evidence against the hypothesized linkage.
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    Notes: Magnetic filtration of labelled cells as a way of separating leucocyte subpopulations was tested with a very simple and easy filtration device, using colloidal magnetite as the labelling reagent. In order to quantitate cell enrichment, a double label (both fluorescent and magnetic) was used, under conditions which labelled less than 10% of the cells in the initial sample. Up to 20 million cells were simply passed through a small magnetic filter with a hand-held syringe. Depletion of labelled cells in the suspension that passed through was threefold, and enrichment of labelled cells in the wash of the filter after its removal from the magnet was approximately fivefold. Factors which limited the quality of separation are discussed. Other, more preliminary, experiments found enrichments of 15–to 30-fold with the same colloidal magnetite and hand-held apparatus when the cell labelling system was more selective.
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: HLA class I phenotyping was performed using T-lymphocyte populations isolated by immunomagnetic beads (IMBs) coated with monoclonal antibodies with specificity for CD2, CD4 or CD8. The results were compared to those obtained using density gradient-separated lymphocytes (PBL). The typing trays were read by the automated simultaneous double-fluorescence (SDF) technique previously established in our laboratory using an Astroscan 2100 system. The aims of the present study were to establish whether the advantages of IMB lymphocyte separation and automated plate reading by SDF were complementary and whether the results obtained by IMB-SDF and PBL-SDF were concordant.Similarity coefficients for paired results obtained by IMB-SDF and PBL-SDF varied between 0.825 using anti-CD8-coated IMBs and 0.914 using anti-CD4-coated IMBs with a consistent excess of stronger results observed with the PBL-SDF technique. The variations observed did not result in incorrect phenotype assignment but would significantly influence a cross-matching test.These results illustrate the feasibility of using IMB-separated lymphocytes for HLA phenotyping by SDF.
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: Langerhans cells (LC) play an important role in the skin immune system. They are bone marrow-derived and function as the only accessory and antigen-presenting cells in the skin. Several techniques for enriching these cells have been devised, and four, including density gradient centrifugation, use of cell sorter, panning and immunomagnetic separation, are discussed. It is concluded that the most satisfactory method for isolation of LC is based on density gradient centrifugation and the most satisfactory for depletion of epidermal cell preparations for LC is based on the immunomagnetic principle.
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  • 77
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    International journal of immunogenetics 16 (1989), S. 0 
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    Notes: The bifunctional cross-linking reagent dithiobis (succinimidyl propionate) (DSP) was used to cross-link 125I surface-labelled glycoproteins from viable thymocytes. The cells were solubilized, and the cross-linked material immunoprecipitated and analysed by SDS-PAGE. When DSP cross-linked thymocyte material was immunoprecipitated with either anti-ThB or anti-Ly 5 monoclonal antibodies, and then cleaved, molecules with masses identical to Ly 5 (Mr180 kD) and ThB (Mr 16–18 kD) were obtained. However, if the cross-linker was not cleaved, the intact product had a molecular mass of 〉 200 kD. The identity of these co-precipitated, cross-linked moieties was formally proved by limited proteolysis peptide map analysis. The data indicated that the ThB and Ly 5 antigens were associated on the thymocyte cell surface but no such association could be found on peripheral lymphocytes. The ThB-Ly 5 interaction may indicate an association relevant to the differentiation of thymocytes.
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    Notes: ABH and related antigens appeared a long time ago in the evolution of vertebrates on tissues in contact with the external environment, which suggests that the polymorphism given by these antigens might play a role in the relationships of the species with pathogens. However, they are also oncodevelopmental markers and some recent experimental data suggest that they might play a role in cell-cell recognition at some stages of development. This type of function is difficult to reconcile with the polymorphic nature of these markers unless one considers that the glycosyltransferases necessary for the synthesis of the active structures are encoded by various members of multigene families. Some non-polymorphic members of the families would have their expression limited in time and space during development, leading to the same antigenic patterns in every individual, and these could reappear in some tumours, while the expression of other polymorphic members (A/B/O, H/h, Se/se, Le/le), leading to a variety of antigenic phenotypes, would be expressed at later stages and remain so during the whole life of the individual. The corresponding antigens could disappear from some cancer cells. It is argued that the ABH and related antigens would have primarily been involved in cell-cell recognition phenomena. The polymorphism would have evolved later from gene duplication under environmental pressure, the expression on erythrocytes which occurred very late in evolutionary time probably being of very little biological significance.
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  • 79
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    International journal of immunogenetics 15 (1988), S. 0 
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    Notes: IgA2 serum levels were measured by ELISA in 120 healthy subjects from 40 nuclear families (both parents and one offspring). No sex-associated difference was observed. Moreover, the IgA2 serum levels proved to be significantly correlated in parent-offspring pairs (r=0·55; P 〈 0·001), while there was no significant correlation in mother-father pairs of the same family. The data suggest that the serum level of the IgA2 subclass is genetically controlled.
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    International journal of immunogenetics 15 (1988), S. 0 
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    Notes: We have utilized a group of MHC class I genes produced by in vitro recombination between Dp and Dd to study recognition of MHC class I molecules by cytolytic T cells (CTLs). Both polyclonal allo-specific and H-2-restricted CTLs require that α1 and a2 of the target class I molecule be derived from the same haplotype for efficient killing. By using T-cell lines we showed that within the bulk population there must exist a fraction of T cells which can recognize epitopes in al or α2. Critical residues for T-cell recognition have been identified using these chimeric genes.
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    Notes: Transplantation tolerance was induced in mice by inoculating newborn animals with semi-allogeneic haematopoietic cells. The mice rendered tolerant were treated within the first week of birth, or at the time of grafting (age 7–8 weeks), with recombinant interleukin-1 (rIL-1) or interleukin-2 (rIL-2). The effects of these treatments on tolerance induction were monitored in terms of skin allograft survival. Treatment of newborn mice with rIL-2 abolished tolerance induction in nearly all tested animals. When administered at the time of grafting, both rIL-1 and rIL-2 decreased the proportion of tolerant animals. However, these modulation effects of interleukins were only observed in strain combinations with genetic differences at the K end of H-2 or in the entire H-2 complex, in which it is difficult to establish permanent tolerance; no effects of interleukins on tolerance induction were found in a strain combination with a relatively weaker genetic barrier represented by incompatibility at the D region of the H-2 complex.
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    International journal of immunogenetics 14 (1987), S. 0 
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    Notes: An example of red cells having no reaction with any Rh antisera was found in a Japanese woman. Results of a serological investigation of the family indicated the action of a ‘regulator’ gene. Her serum contained an antibody which agglutinated all cells of common Rh types, except for Rhnull, by the saline, anti-globulin and papain techniques.
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    International journal of immunogenetics 14 (1987), S. 0 
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    International journal of immunogenetics 14 (1987), S. 0 
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    Notes: Antigen-specific helper factor (ASHF), a soluble product of T helper (Th) cells, binds antigen and can induce B-cell and cytotoxic T-lymphocyte (CTL) differentiation. Its relationship to the T-cell surface antigen receptor (TcR) is unknown. Both have MHC-restricted recognition of nominal antigen, thus they may share very similar combining sites. Using monoclonal anti-TcR to imrnunoprecipitate partially purified ASHF, we have obtained evidence for shared determinants between ASHF and the TcR. Antigen affinity-enriched supernatants of a Th clone, LB19, are functionally active in antigen-specific, help-dependent CTL assays. FPLC anion exchange salt fractions of these supernatants were 125I-labelled and immunoprecipitated with KJ16.133 monoclonal anti-TcR coupled to Sepharose 4B. Precipitates were analysed by SDS-PAGE. We have obtained clear evidence that functionally active Th culture supernatants contain molecules specifically precipitable by anti-TcR antibody.
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    Notes: Serum IgG antibodies to ovalbumin (OA) and beta-lactoglobulin (BLG) were quantified by ELISA techniques in 22 monozygotic (MZ) and 24 dizygotic (DZ) healthy twin pairs. Antibody levels were comparable in the MZ and DZ groups both for anti-OA and anti-BLG antibodies. The genetic variance (ĜWT) was 0.167 for log IgG anti-OA antibodies, and 0·173 for log IgG anti-BLG antibodies, with heritability estimates of 0·44 and 0·37, respectively. No indication was observed of genotype–environmental interaction or differential environmental covariance for the log antibody levels in the MZ and DZ twins. The anti-OA and anti-BLG antibody levels in the same individual correlated only to a low degree. The levels of naturally occurring serum IgG antibodies are significantly influenced by genetic factors.
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    Notes: The relationship between the immunoglobulin kappa light chain allotypes and autoantibodies was studied in a series of seven human monoclonal kappa-bearing IgM antibodies with Rheumatoid Factor (RF) activity, two IgM anti-low density lipoprotein (LDL) antibodies, and one IgM anti-intermediate filament (IF) antibody. Residues at amino acid positions 153 and 191 related to the Km allotypes in human kappa chains were determined by an HPLC tryptic fingerprint and corroborated by amino acid sequence analysis. All the autoantibodies shared similar variable regions derived from the V gene(s). The seven RF and the anti IF were associated with the Km(3) constant region allotype whereas the two antiLDL were associated with the Km(1,2) allotype. Thus, monoclonal autoantibodies showed the same Km allotypic distribution as the normal population. However, although the number of samples is small, it seems likely that a preferential association may exist between particular V, genes and Km alleles in the generation of autoantibodies with different specificities.
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    International journal of immunogenetics 13 (1986), S. 0 
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    International journal of immunogenetics 15 (1988), S. 0 
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    Notes: Staphylococcal enterotoxin B (SEB) is a T cell mitogen with properties different from the plant lectin mitogens. We examined the stimulation of mitogenesis induced by SEB in BALB/c mouse spleen cells and its relationship to major histocompatibility complex (MHC) and related cell surface proteins. Based on the ability of specific monoclonal antibodies to block mitogenesis, SEB stimulation appears to be more dependent on interaction with I-E than with I-A class II MHC molecules. Additionally, anti-L3T4, and possibly other antibodies specific for proteins related to the T cell receptor complex, were inhibitory. When A20 cells were treated with SEB and used to stimulate BALB/c spleen cells which were not otherwise exposed to SEB, the treated A20 cells were capable of stimulating mitogenesis of the BALB/c spleen cells. The data support the hypothesis that SEB stimulation is mediated primarily by interactions with class II MHC proteins and possibly proteins in the T cell receptor complex. We also observed that the presence of SEB in DBA/2 (Mlsa)-stimulated BALB/c (Mlsb) spleen cell cultures enhanced the BALB/c mitogenesis three-fold over the sum of the SEB- plus Mls-stimulated mitogenesis. These results suggest that SEB may be a useful tool for further exploration of the Mls response.
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    Topics: Biology , Medicine
    Notes: In the formation of a repertoire, T cells are selected through a window of autoreactivity which is defined by a low boundary representing the minimal autoreactivity required to enter the T-cell compartment and a high boundary which determines the highest admissible autoreactivity. We propose that the Mls gene product down regulates autoreactivity and thus modifies the formation of the T-cell repertoire. Given the polymorphism of Mls and the assumption that Mlsb is more inhibitory than Mlsd, it is conceivable that Mlsb (responder) mice admit into their T-cell compartment T cells with higher autoreactivity than Mlsd mice. We suggest that it is this highly autoreactive fraction of Mlsb T cells which responds in the overt Mls response. We show that Mls tolerance eliminates T cells responding in the overt Mls response but not T cells responding in the latent Mls response. This is consistent with the finding that T cells responding in the latent Mls response occur in Mlsb as well as in Mlsd mice.
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  • 92
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 13 (1986), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 93
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 13 (1986), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 94
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 13 (1986), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The classification of antigens into TD, TI-1 and TI-2 varieties raises the question of whether responses to these antigens are produced by distinct or identical subpopulations of B cells. In the present study we have examined the extent of intraclonal specificity variation in the progeny of PFC appearing after stimulation with two unrelated antigens. Mouse lymphoid cells were stimulated with pairs of TD and TI antigens, PFC were individually cultured and daughter PFC examined for their specificity. In all combinations used, PFC responding to TD antigen engendered, after 48 h of culture, a high frequency of PFC daughters expressing one or the other antibody specificity, notwithstanding the specificity of parental PFC. However, PFC responding to TI antigens seemed less subject to variation in specificity, and PFC daughters engendered after a 48 h culture period were, in the majority, of the parental specificity. These results are analysed in relation to different subpopulations of B cells.
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  • 95
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 14 (1987), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 96
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 14 (1987), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: An association of HLA-DR5 and goitrous autoimmune thyroiditis has been reported elsewhere (Farid et al., 1981; Weissel et al., 1980). Recently, the disease was found to be associated with HLA-DR4 in Newfoundlanders (Farid & Thompson, 1986). In order to find out whether different HLA associations with the disease may be found in different ethnic groups, we have now typed 68 patients with autoimmune goitrous thyroiditis from Eastern Hungary for HLA-A, -B, -C, and -DR antigens; 66 of these patients were also typed for IgG heavy-chain markers (Gm). A significant increase in DR3 (OR = 3·30) and a non-significant increase in DR4 (OR = 1·67) were found in the patients when compared with controls. The Gm3 allele, g, interacted with DR3 to enhance the risk for goitrous autoimmune thyroiditis. Hashimoto's disease may show different associations in different ethnic groups, and indeed within the same ethnic group, when newly diagnosed patients are typed several years apart.
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  • 97
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 14 (1987), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Book reviewed in this article:J. W. Goding: Monoclonal antibodies: Principles and Practice. Production and Application of Monoclonal Antibodies in Cell Biology, Biochemistry and Immunology.W. I. Morrison (Ed.): The Ruminant Immune System in Health and Disease.
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  • 98
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 14 (1987), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 99
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 14 (1987), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Pregnant mice from the congenic strains C57BL/10Sn, B10.BR, B10.A/SgSn, B10.A(SR)/SgSn, B10.A(2R)SgSn and B10.A(18R)Sg were fed Purina Laboratory Chow or the same diet plus approximately 400IU vitamin A daily and given 80 mg/kg dexamethasone intra-peritoneally or a sham injection on the 12th day of pregnancy. It was found that only strains with b alleles between H-2S and H-2D had significantly higher frequencies of isolated cleft palate among their progeny when fed the supplemental vitamin A. The locus appears to be on the centromeric side of a dexamethasone-induced cleft palate gene which has been mapped to the same general area.
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  • 100
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 14 (1987), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Antigen-specific T-cell helper factors were secreted from a (T,G)-A—L specific T-cell line and clones. The factors were released upon antigenic stimulation and could be induced by a low or a high dose of antigen. The factors secreted upon low-dose stimulation possessed the antigenic specificity of the secreting cells, while the high dose-induced factors had a broader antigenic specificity and could react with the closely related polypeptide (Phe,G)-A—L, even when the cells were restricted to (T,G)-A—L. Both the low dose- as well as the high dose-induced factors could not trigger antibody production in the presence of a non-relevant antigen, and did not collaborate with B cells immunized with a non-related antigen for the production of antibodies. The helper factors, like their secreting cells, were H-2-restricted in the collaboration with B cells. In contrast to the helper cells, however, they did not require accessory cells for triggering the B cells in the process of antibody production. Some preparations of helper factors were found to be inactive. The helper activity could be restored by IL-2. Thus, IL-2 is an additional essential factor required for the antigen-specific collaboration of B cells and T-cell helper factors.
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