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  • 1
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The aim of this study was to determine immunogenetic markers of susceptibility in Crohn's disease (CD), taking the different features of the clinical course of the disease into account. HLA class I, HLA class II and TAP transporter gene polymorphisms were studied using DNA typing methods. Gene and antigen frequencies were analysed and compared in a group of 102 CD patients and 200 unrelated healthy controls from the same area. Analysis of the whole CD patient population revealed no definite association with either HLA or TAP gene alleles, with the exception of an association with DRB1*1302 (Pc 〈 0.05). However, when clinical subgroups of patients were considered, specific associations with some genetic markers were found. The most definitive results involved a genetic association in the group of patients who did not respond to glucocorticoid therapy. This group was characterized by a high frequency of HLA-DRB1*04 (P 〈 0.05). Conversely, a positive association with the TAP2-A allele was found in cortico-responder patients (Pc 〈 0.03). Furthermore, analysis of the distribution of HLA class II alleles in relation to the presence of extra-intestinal manifestations revealed an association with the DQB 1*0501 or *0503 suballele of DQ5 (P 〈 0.05). Finally, patients with lesions in the small bowel were more frequently HLA DRB1 *07 (P 〈 0.05). The present study supports the concept of clinical heterogeneity in Crohn's disease associated with a background of genetic heterogeneity.
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  • 2
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 23 (1996), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Serological HLA types (A, B, C, DR and DQ loci) were studied in five different Indian tribes (Cubeo, Tucano, Coreguaje, Embera and Noanama) belonging to two distinct linguistic families. For all the MHC loci, the range of variation among the five tribes was enormous. Two tribes, Cubeo and Tucano, showed a wide spectrum of antigenic specificities which seemed to be due to admixture from non-tribal groups, while in the other three tribes the polymorphisms of various HLA loci showed restricted distributions. The gene frequency data, when converted to a kinship matrix and a two-dimensional eigenvector plot, indicated that members of the same linguistic family tend to have greater genetic affinity.
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  • 3
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 23 (1996), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We describe a method for rapid matching of HLA-A, -B and -C allotypes using simultaneous polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and heteroduplex analysis. Electrophoresis is performed at ambient temperature without requirements for buffer cooling. SSCP and heteroduplexes are revealed as discrete spatially separated band clusters. Using HLA-A, -B and -C locus-specific PCR primers, matching for alleles at these loci can be performed in 5h. We tested 17 serologically matched patient-unrelated donor pairs and found considerable microheterogeneity at the DNA level. We propose that this technology has several advantages over conventional low-resolution typing methods and represents a potentially valuable screening method in unrelated donor selection.
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  • 4
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 23 (1996), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 5
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    International journal of immunogenetics 23 (1996), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 6
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 22 (1995), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Investigation of pairs of unrelated persons mismatched for a particular HLA-DQB1 or -DPB1 gene on the induction of cytotoxic T lymphocytes (CTL) revealed that HLA-DQ and HLA-DP antigens provided a slight proliferative stimulus which was, however, sufficient for the generation of CTL. Monomorphic anti-DQ and anti-DP monoclonal antibodies abrogated the induction of cytotoxic response. The results indicate that the HLA-DQ and HLA-DP antigens play a similar role to HLA-DR specificities in clinical bone marrow transplantation.
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  • 7
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 22 (1995), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 8
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: A negative association between insulin-dependent diabetes mellitus (IDDM) and HLA-DR, DQA1 or DQB1 was found in a large population-based investigation of childhood-onset patients (more than 420 patients) and controls (more than 340 controls) from Sweden. The relative risk was decreased for several haplotypes that were negatively associated with IDDM: DR15-DQA1*0102-DQB1*0602, DR7-DQA1*0201-DQB1*0303, DR14-DQA1*0101-DQB1*0503, DRI1-DQAI*0501-DQB1*0301, DR13-DQA1*0103-DQB1*0603 and DR4-DQA1*0301-DQB1*0301. In a relative predispositional effect (RPE) analysis, however, only the DR15-DQA1*0102-DQB1*0602 haplotype was significantly decreased, which suggests that the major protective effect for IDDM is carried by this haplotype. This was supported by the observation that all genotypes which were negatively associated with IDDM, except DR7/13, included at least one allele from the DR15-DQA1*0102-DQB1*0602 haplotype. Relative predispositional effect (RPE) analysis of genotypes showed further that the DR15-DQA1*0102-DQB1*0602 haplotype was also negatively associated with IDDM when combined with any other haplotype, whether negatively or positively associated with IDDM. This supports previous suggestions that DR15-DQA1*0102-DQB1*0602 acts dominantly. However, both the stratification and the predispositional allele test failed to distinguish the negative association between IDDM and DR15 from that of DQBT0602. On the other hand, these tests indicated that DQA1*0102 was not likely to explain the negative association between IDDM and the DR15-DQA1*0102-DQB1*0602 haplotype. We conclude that the
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  • 9
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 22 (1995), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: A reliable method for high-resolution HLA-DRB1 typing using the combination of group-specific amplification and RFLP analysis is described. Group-specific PCR amplification (multiplex ARMS-PCR) was carried out under the same conditions for all groups using seven different primer pairs divided into four groups: (1) DR1 and DR10; (2) DR2, DR7 and DR9; (3) DR3, DR5, DR6 and DR8, and (4) DR4. The subsequent polyacrylamide gel electrophoresis was used to determine the group(s) contained in each sample. DR1, DR2/7, DR3/5/6/8, DR4, DRB1*0901 and DRB1 * 1001 could be distinguished easily using this system. Computer analysis of the various restriction enzyme cleavage sites was carried out on 105 DRB1 allele sequences. It was shown that all DRB1 alleles, except for five allele pairs and some alleles possessing silent mutations, could be distinguished with commonly available restriction endonucleases. Computer analyses on the discrimination of the heterozygous and homozygous combinations were also carried out. Although some heterozygous combinations could not be distinguished with single digestion, double digestion using two restriction enzymes could distinguish most of such heterozygotes. The results of the typing of 100 Japanese individuals using this method showed good agreement with those obtained by other methods.
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  • 10
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    International journal of immunogenetics 22 (1995), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: IgA deficiency (IgA-D) represents the most common immunodeficiency syndrome of infancy. In most cases IgA-D represents an isolated immunological disorder, while sometimes it is associated with IgG subclass deficiency or with the presence of autoantibodies. We investigated the pattern of association of IgA-D with DRB1 and DQB1 loci of the HLA region by DNA molecular typing, which allows the identification of previously serologically undefined specificities. We also compared the gene frequency of DRB1 and DQB1 allelic variants between IgA-D subjects with or without serum autoantibodies. Our results indicate that the gene frequency of the DRB1*0102 subtype and of the DRBP0102, DQB1*0501 haplotype is significantly higher in IgA-D than in the general population. Furthermore, the IgA-D subjects with autoantibodies showed a positive association with DR4 and DR13 subtypes, thus supporting the hypothesis that genetic factors are also involved in the association between IgA-D and autoantibodies.
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  • 11
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 22 (1995), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Fifteen samples of non-tumoural breast tissue, 24 cases of benign lesions, four biopsies of inflammatory carcinomas and 94 tumour samples of primitive mammary carcinomas were analysed for HLA class II expression. We found, first, that HLA class II antigens were detectable in all cases of non-neoplastic breast tissue. Secondly, HLA class II antigen expression was notably increased in benign neoplasms and hyperplastic lesions. In contrast, only 32 out of 94 carcinomas showed expression of HLA-DR antigens, 17 tumours had HLA-DP antigens and 11 carcinomas were positive for the presence of DQ molecules. The expression of class II antigen was associated with the degree of histological differentiation (P 〈 0.05) but was independent of stromal leucocytic infiltration. Thirdly, HLA-DR was very strongly expressed in intravascular tumoural thrombi, especially in the ‘inflammatory carcinomas’. The immunephenotype of inflammatory infiltrate was analysed in benign and malignant lesions. In malignant lesions the mean number of inflammatory cells was significantly higher than in benign lesions. Interestingly, we found no differences in the amount and composition of inflammatory infiltrate between HLA-DR positive and negative tumours.
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  • 12
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 13
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 22 (1995), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
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  • 14
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Nineteen horse MHC class I specificities have been serologically identified previously at a single locus (ELA-A), and two other specificities appear to be coded at other loci. Biochemical studies indicate that there are at least two expressed loci. In order to establish the number of transcribed horse MHC class I genes, we made a cDNA library from a heterozygous animal (ELA-A3/A7), and screened for positive clones using a bovine class I probe. More than 200 class I clones were isolated in this way, and so far seven unique full length sequences have been identified. All of the sequences are predicted to code for surface expressed, functional molecules. The number of different sequences identified demonstrate that at least four genes are transcribed, although variations in transmembrane length (which is generally conserved in class I loci) suggest that five genes could be represented. Evolutionary analysis of these sequences (and two additional sequences known to represent different horse class I loci) reveals no firm relationships, such that the division between the different loci cannot be discerned. These results suggest an unusual evolutionary history for the horse MHC, the precise nature of which may be revealed only following further cross-species comparisons.
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  • 15
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 22 (1995), 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 22 (1995), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We studied the allelic constitution at the HLA class II DQA1, DQB1, DRB1 and DPB1 in 94 Italian multiple sclerosis (MS) patients and 98 controls. No significant increase in the frequency of DR2 alleles was detected among MS patients, as previously observed both in European and some Italian studies. A slight increase was found for the DQA 1*0301 and DQB 1*0602 alleles in the MS patients. No significant association was found with the glutamine residue at position 34 of the DQ α chain, which was noted previously in MS patients from northern Europe.
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  • 17
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Fifty-two British and 29 Greek idiopathic membranous nephropathy (IMN) patients were analysed for DRB, DQA1, DQB1 and DPB1 gene polymorphism using second exon amplification and sequence-specific oligonucleotides (SSO). In addition 100 British and 92 Greek controls were analysed.A highly significant increased frequency of the DRB 1*0301 allele was found in IMN patients from Britain (80%), when compared to controls (27%, OR 10.6, P= 0.000004). A lower frequency of DRB 1 *0301 was observed in Greek IMN patients (33%), but this was just significant before correction, when compared to Greek controls (15%, OR 3, P= 0.02). The DRB3 allele most often associated with DRB 1 *0301 was DRB3*0101 (OR 4.2, P= 0.00025) in British patients and DRB3*0201/2 (OR 11, P=0.006) in Greek patients. In Greek IMN patients a decrease in DR16 was found (OR 0.08, P=0.004), and the overall incidence of DR2 was significantly lowered when both sets of IMN patients were combined (OR 0.21, χ2 17.6, P= 0.00013).The incidence of DQA1 *0501 was raised in both Greek (96%vs. 66%, OR 9.7, χ2 6.9, P= 0.009) and British IMN (85%vs. 45%, OR 7.4, χ2 20, P= 0.00007) patients. This gives some support to a proposal for a major role for this allele in IMN. However, DQB1 *0201 was also raised in both Greek (50%vs. 21%, OR 3.6, χ2 8.1, P= 0.005) and British (90%vs. 44%, OR 10, χ2 21.7, P=0.00004) IMN patients. The DQA1*0102 allele was significantly lowered in Greek IMN patients (15%vs. 32%, OR 0.05, 12.2, P=0.0008), probably reflecting a lowering in the DR16 haplotype. No significant difference was observed in the frequencies of DPB alleles in patients and controls.It is concluded that DRB 1*0301 has the strongest association with British Caucasoid IMN. The Greek Caucasoid IMN association with DRB 1*0301 is weaker, and a role for other alleles has not been eliminated.
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  • 18
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    International journal of immunogenetics 22 (1995), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: HLA polymorphisms of class I and class II MHC were investigated in 40 Kuwaiti vitiligo patients and in 40 controls using microcytotoxicity assay. HLA-B21, Cw6 and DR53 were increased significantly in patients compared to controls (P= 0.00001, 0.00001 and P= 0.0053 respectively) while HLA-A19, DR52, were significantly decreased (P= 0.00236,0.05, respectively). Total T-cells, T4 and T8 were measured as CD2, CD4 and CD8 respectively by flow cytometry. Vitiligo patients showed significant increase in CD4 compared to controls (P= 0.03). Our findings suggest that HLA-B21 and Cw6 and DR53, are susceptible genes of vitiligo, while A19 and DR52 are protective genes in the Kuwaiti population.
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  • 19
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    International journal of immunogenetics 22 (1995), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We propose to use the extreme diversity of HLA in order to detect, by anonymous check, double registration on computer files, of patients waiting for organ transplantation. A simulation on a panel of 69461 unrelated individuals, caucasoid, confirms the relevance of the method.
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  • 20
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Five human teratoma cell lines have been characterized for the presence of a certain number of marker antigens whose presence or absence has been shown to be characteristic of mouse embryonal carcinoma (EC) cells. Four out of the five lines have been shown to respond to at least some of the criteria associated with murine EC cells even though only limited in vitro differentiation could be demonstrated. The significance of certain unusual marker antigen combinations present on the cell line Tera I and its clones and so far unobserved for the murine model is discussed. The observation in Tera I populations of cells carrying simultaneously both the F9 and β2-microglobulin or HLA antigens, suggest that the human cell lines may represent a novel material for the study of mammalian differentiation.
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  • 21
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    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 8 (1981), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Principles of Gene Manipulation. Studies in Microbiology
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  • 22
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    International journal of immunogenetics 7 (1980), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: A healthy 22-year-old woman was noted to have erythrocytes of the Pk phenotype: a strong Pk antigen, no detectable P antigen and anti-P antibody in her serum. Her erythrocytes contained four to six times as much Pk glycolipid (globotriaosylceramide or CTH) and approximately half as much P glycolipid (globotertraosylceramide or globoside) as normal red cells. The structures of CTH and globoside were characterized by analysis of permethylated sugars and complement fixation in addition to chromaographic mobility and sugar composition. Inasmuch as the erythrocytes of two Pk individuals that were analysed previously (Marcus et al., 1976) contained no detectable globoside, these abnormalities appear o represent a new phenotype in the P blood group system.
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  • 23
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    International journal of immunogenetics 7 (1980), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We studied 201 unrelated French Basque individuals for HLA and Bf polymorphisms. The haplotypes of eighty-seven of them were deduced from family studies. The results show the frequency of the Bf F1 allele (0.1393) which is the highest one currently reported. They confirm the high frequencies of HLA-Aw19.2 and B18 previously reported in that population and show that a whole haplotype with strong linkage disequilibria, namely Aw19.2, Cw5, B18, Bf F1, DRw3 is frequent. On the other hand, the gene frequency of Bf S is decreased (0.5497) as compared with the other European Caucasoïd populations, while a slight increase in the Bf F gene frequency (0.2960) appears. These results point out that it is of importance to consider the genetic background in choosing the population where linkage disequilibria are to be studied.
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  • 24
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    International journal of immunogenetics 7 (1980), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The genetic control of hybrid resistance to BALB/c fibrosarcoma Meth-A was investigated. A Meth-A tumour grew slower in (BALB/c X C57BL/6)F1 and reciprocal hybrid mice than in syngeneic BALB/c mice and was also found to grow slower in females than in males. Significant F1 resistance was demonstrated after both subcutaneous and intraperitoneal injection of tumour cells. However, (BALB/c X DBA/2)F1 mice did not show any significant resistance to Meth-A. In H-2 linkage studies of [BALB/c X (BALB/c X C57BL/6)] backcross mice, no statistically significant differences in the resistance of H-2 heterozygotes and homozygotes to Meth-A were observed. These results indicated that F1 hybrid resistance to Meth-A was controlled by non-H-2-linked resistance factor(s). No linkage was observed between resistance to Meth-A and coat colour c- and b-loci.
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  • 25
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Serological and genetic analyses of H-2 antigens indicate that each K or D region allele controls two highly polymorphic antigenic sites, the alpha site corresponding to the private specificity and the gamma site corresponding to the long public specificities. Studies of cell surface distribution and biochemical characteristics of the alpha type specificity H-2.4 and gamma type specificity H-2.28 in the product of a D region allele, Dd, demonstrate that these specificities are carried on two different polypeptide chains. Accordingly, two distinct and polymorphic genes are postulated to code for the product controlled by the D region of H-2.
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  • 26
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    International journal of immunogenetics 2 (1975), S. 0 
    ISSN: 1744-313X
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  • 27
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    International journal of immunogenetics 2 (1975), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Twenty-six combinations of C57BL/10 congenic mice involving incompatibilities in the I region and the H-2K or H-2D regions of the major histocompatibility complex were studied in a cell-mediated lympholysis assay (CML). All combinations were positive; however, six were unidirectional. Three of these were consistent with the mapping of an effector cell stimulating locus (ECS) between the IB and IC sub-regions. Possible reasons are given for the negativity of CML in I/H-2K or H-2D region incompatible combinations. A statistical method used to analyse the data is described.
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  • 28
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: H-2 typing of two inbred mouse strains, GRS I/A and LIS/A, revealed that they both carry the same, previously unknown haplotype, designated H-2dx. The H-2dx haplotype has the K region allele identical or very similar to that of H-2d, however it differs from H-2d at the I region genes and has none of the D region alleles previously described in inbred mouse strains.When the H-2dx haplotype was used in F1 complementation tests, it failed to prevent rejection of B10.D2 skin grafts by (GR × B10.A)F1 and (LI × B10.A)F1 recipients, as well as rejection of R103 grafts by (GR × 2R)F1, (LI × 2R)F1, (GR × B10)F1, and (LI × B10)F1 recipients. In all these combinations, the donor and the recipients were matched at the K and D regions, but differed at the I region. The mean rejection time was 12 days (beginning) and 15.9 days (end of rejection).The second set skin grafts were rejected at approximately the same speed as the first set skin grafts, and after their rejection a cytotoxic antibody, most likely anti-Ia, was found in the serum of the recipient mice. The absence of accelerated second set skin graft rejection in the I region incompatibility observed in these experiments is in sharp contrast to the extremely fast rejection of K or D region incompatible second set skin grafts. This lack of demonstrable anamnestic response is either due to the presence of enhancing antibodies, or to an inherently inferior capacity of I region incompatibility to elicit, in vivo, an effective anamnestic response.
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  • 29
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    International journal of immunogenetics 2 (1975), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The CBA/H mouse lymphocytes which divide when cultured together with allogeneic blood in mixed lymphocyte reactions (MLR) have been shown to be mainly of thymic origin with the aid of thymus grafted radiation chimaeras. By adaptation of a system used previously to quantity mitogen responsive cells, the relative number of cells in CBA/H mouse blood capable of responding in the MLR, and the effects of preimmunizing CBA/H mice with allogeneic cells have been quantified. In mixed lymphocyte reactions between parental and allogeneic F1 hybrid cells, substantial numbers of the latter cell type have been found in division. Attempts to elucidate the nature of these reacting F1 cells indicate that they are probably mainly of bone marrow origin and that they are responding in a non-specific manner.
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  • 30
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    International journal of immunogenetics 2 (1975), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The immunogenicity of Thy-1 antigens was examined using the Thy-1 congenic mouse strains A and A/Thy-1.1. A disequilibrium of response was found between these strains. A strain mice rejected skin grafts and produced high titres of antibody to lymphoid cells from A/Thy-1.1 strain mice. However, in the reverse combination grafts were not rejected nor was there any significant antibody response. A/Thy-1.1 mice did not respond to Thy-1.2 antigen when it was presented on an H-2 allogeneic background (A·SW strain) but did respond to it when non-H-2 incompatibilities were involved (B10·A strain donor). We postulate the existence of Ir gene(s) for the response to Thy-1.2 antigens which are linked to H-2. The failure of A/Thy-1.1 strain mice to respond to Thy-1.2 antigens in the absence of carrier determinants is the result of a deletion (in the germ line) of the appropriate Ir gene itself resulting from the long association of the H-2a haplotype of the A mouse (donor of the genetic background of A/Thy-1.1 strain) with the Thy-1.2 gene.
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  • 31
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    International journal of immunogenetics 2 (1975), S. 0 
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  • 32
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    International journal of immunogenetics 2 (1975), S. 0 
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    Notes: A survey has been carried out on sera from 136 myeloma patients for distribution of Gm markers 1, 2, 4 and 12 and Inv 1. It was found that with Gm (1), Gm(2) and Gm (12) the distribution was normal. However, Gm (4) was found to be present in 41 % of the sera compared with an expected value of 90%.
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    International journal of immunogenetics 7 (1980), S. 0 
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    Notes: CBA/N mice have an X-linked B cell defect which prevents them from responding to non-mitogenic thymic independent (TI-II) antigens such as dinitrophenylated (DNP-AGG) Ficoll. The F1 male progeny of CBA/N female mice express the same defect. Spleen cell suspensions from such defective mice (CBA/N X C3H/HeN F1 males) could not respond to DNP-AGG-Ficoll following in vitro immunization and subsequent transfer into irradiated, syngeneic, F1 male recipients as expected. In contrast, normal CBA/N X C3H/HeN F1 female spleen cells could respond and effect a ‘rescue'; they mounted strong plaque-foriming cell 7 days after in vitro exposure to DNP-AGG-Ficoll and subsequent transfer into irradiated F1 male recipients. Defective F1 male spleen cells could bind significant quantities of DNP-AGG-Ficoll, however, after, in vitro exposure. Extensive washing of these spleen cells could not reverse this binding. Such DNP-AGG-Ficoll-exposed and washed F1 male spleen cells could, after transfer, aid normal untreated F1 female cells in their rescue function. The defective F1 male spleen cells could convey immunogenic quantities of DNP-AGG-Ficoll to the ‘rescuing’ F1 female cells.Mitomycin treatment of F1 male cells did not interfere with their conveyor function. Goat anti-mouse μ serum impeded the passive antigen conveyor function of defective F1 male cells as did prior exposure to high concentrations of free DNP-AGG hapten. Our data support the view that the B cell defect of CBA/N X C3H/HeN F1 male mice does not relate to antigen binding, but rather to an inability to be effectively triggered by certain cell-bound polymeric antigens.
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  • 34
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    International journal of immunogenetics 2 (1975), S. 0 
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    Notes: A group of Australian aborigines with a high frequency (15.5%) of asymptomatic Australia antigen (Au) carriers shows a statistically significant deficiency of W15 among Au carriers. The association was observed during an HL-A survey, and was confirmed by a further study designed to investigate the observed association. Further, the pooled data establish the association.The observed association can be explained satisfactorily in terms of an Au immune response locus closely linked with, and having alleles in linkage disequilibrium with alleles of, the Four locus of the HL-A system. Since a deficiency of W15 among Au carriers has been reported in a northern European study, though it has not been observed in others, it is argued that the association has not occurred by chance, but that selection involving both HL-A and immune response genes has been responsible for the observed association.A significantly high proportion of Au carriers were observed to be homozygous for antigens of the Four series. The data, and their interpretation, lend support to the proposition that asymptomatic Au carriers are homozygous for an inactive allele of the gene responsible for the immune response to Au.
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  • 35
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    International journal of immunogenetics 2 (1975), S. 0 
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    Notes: Xenoantisera were raised in New Zealand white rabbits by immunizing with red blood cells from the S5B (Ag-B1) and ALB or BUF (Ag-B6) strains of inbred rats. By appropriate absorptions, specific Ag-B1, but not Ag-B6, reagent antiserum could be made. The anti-Ag-B antibodies required Ficoll as a diluent for haemagglutination, implying that they are IgG.
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    Notes: A report is presented of three cases of healthy individuals with a transient absence of HL-A2 antigen and presence of W28. Temporary deletion of platelet-specific antigen 1a was observed in eight normal blood donors. The cause of the phenomenon is discussed.
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  • 38
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    International journal of immunogenetics 7 (1980), S. 0 
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    International journal of immunogenetics 7 (1980), S. 0 
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    Notes: Results of a population study with all currently available B-cell specific alloantisera indicate that eight antigens controlled by the RhLA-linked DR locus can now be identified. This leaves a gene frequency of about 0.15 for unidentified or ‘blank’ antigens of that locus. Of the nine identifiable la antigens which are not controlled by the DR locus, three or four may form the basis of a second series which is probably also controlled by the RhLA region.
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    International journal of immunogenetics 7 (1980), S. 0 
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    Notes: Induction of tolerance to bovine serum albumin was studied in mice selected for high (H) or low (L) antibody responsiveness and in their F1 hybrids. No high or low zone tolerances were obtained in H mice whereas L mice were susceptible to tolerance induction by the two schedules. H mice were immunized by repeated injections of tolerogenic BSA for low zone tolerance induction but not after the administration of a single high dose of tolerogenic BSA. Resistance to tolerance induction is dominant in F1 hybrids.
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    Notes: An attempt is made to account for immunoglobulin chain synthesis in terms of genetic events involving IS or controlling elements analogous to those found in bacteria, maize and drosophila. Transposition of variable and constant genes and normal immunoglobulin chain synthesis as well as qualitative and quantitative abnormalities might be explained by such regulatory elements. Intrachromosomal transpositions over short distances would be expressed as apparent hypermutability or redundancy of the variable DNA segment. The constant gene might comprise four sequences coding for the three homology domains and the hinge, separated by intervening sequences. A strong preference for shortrange transposition on the same chromosome and immobilization of the controlling element in the end might account for allelic exclusion.
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  • 42
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    Notes: Fab2 fragments from antisera raised in rabbits with partially purified cellular and serum HLA antigens were tested for their ability to block the cytolytic activity of operationally specific HLA-A, B alloantisera. One Fab2 fragment preparation blocked the cytolytic activity of all the HLA-A,B alloantisera tested; the remaining nine inhibited the lytic activity of alloantisera to certain HLA-A,B allospecificities, suggesting that these xenoantisera contain antibody to certain HLA-A,B allotype determinants or to closely associated structures. In contrast to previous reports in the literature none of the xenoantisera contained significant amounts of antibodies to human β2-microglobulin.
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  • 43
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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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    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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    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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    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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    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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    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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    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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    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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    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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    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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    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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    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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    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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    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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    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 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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    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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    Notes: Studies of 521 sera from the Icelandic cousin marriage project were made to assess the incidence of various anti-tissue antibodies and the levels of immunoglobulins, as these were considered to be useful markers of the humoral immune response. Comparisons were made between these parameters and the HLA-A and B antigens, the blood groups, the immunoglobulin allotypes (Gm, Km and Am), the properdin factor (Bf), and other markers.These investigations offered another approach to the study of the sites of action of immune response genes in man. Because the immune response may be expected to differ for each individual and depend at least in part, on the degree of exposure to different antigens, no absolute correlation was expected. There was, however, a marked association between certain IgG anti-tissue antibodies and HLA antigens. This was most marked for HLA-A10, B18 and B27, but not for HLA-A1 or B8.The comparison of immunoglobulin levels with HLA antigens, was less striking, although HLA-A2 appeared to be associated with low levels of IgE. There were also some associations between immunoglobulin levels and ABO blood groups.
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    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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    Notes: The polymorphism of histocompatibility antigens is usually explained by classical Mendelian laws, which allow the inheritance of one allele per locus. Thus each individual would express two antigens for each locus of the pair of relevant homologous chromosomes, one from each parent.Another explanation is that the structural genes of all the different haplotypes are all in tandem. Regulatory genes would then determine the polymorphism by mimicking Mendelian inheritance–allowing only the relevant gene products for a particular haplotype to be expressed. If correct, one might expect the mechanism to fail sometimes, and silent genes of foreign haplotypes to be derepressed, allowing H-2 antigens of the wrong haplotype to become expressed.In the light of this hypothesis (Martin, 1975; Amos, 1971; Bodmer, 1975; Festenstein, 1978; Garrido et al., 1976a,b), the original findings in our laboratory of extra foreign ‘H-2-like’ determinants on tumour cells passaged in vitro and in vivo with and without virus are considered rather important (Festenstein, 1978; Garrido et al., 1976a,b); not only because they could lead to a better understanding of the genetic basis of MHS polymorphism, but also because of its implication for the surveillance of tumours (Garrido et al., 1976b; Gomard et al., 1977; Blank et al., 1976; Parmiani & Invernizzi, 1975) and microbially damaged cells (Doherty & Zinkernagel, 1975). These extra determinants were tested by various serological techniques and assays of cell mediated immunity.
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    Notes: An investigation of the serological and biochemical properties of red cells in two unrelated British families revealed the probable presence of examples of the rare genotype EnαEn.In one family the En-modified red cells carried N-like determinants associated with s. In the other family M-like determinants associated with S were found.
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    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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    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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    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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    Notes: The lymphocytes from 107 maternal-foetal pairs were examined for their in vitro responsiveness, as determined by the incorporation of tritiated thymidine following stimulation with phytohaemagglutinin (PHA), candida, varicella, mumps, streptokinase-streptodornase (SKSD) and tetanus toxiod. The data were collected and analysed in two sequential groups (forty-seven and sixty) in order to determine whether the results were reproducible. The variable chosen for analysis was the difference (d) between the square roots of the isotope incorporation in the stimulated and control cultures because it gave the most symmetrical distribution of the data. The experimental error in the determination of maternal lymphocyte stimulation was 1.4-8.6% and of the and of the foetal lymphocytes, 1.0-16.6% depending upon the antigen or mitogen and its concentration. The data in the two sets of patients were statistically the same in forty-eight of the fifty-six analyses (fourteen antigen or mitogen concentrations in autologous and AB plasma for maternal and foetal lymphocytes). The statistical limits of the distribution of responses for stimulation or suppression were set by an analysis of variance taking two standard deviations from the mean as the limits. When these limits were translated into stimulation indices, they varied for each antigen or mitogen and for different concentrations of the same antigen. Thus, a detailed statistical analysis of a large volume of lymphocyte transformation data indicates that the technique is reproducible and offers a reliable method for determining when significant differences from control values are present.
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    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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    Notes: Epa-1-specific cytotoxic T lymphocytes (CTL) lyse epidermal cells (EC) of different Epa-1+H-2k strains, such as AKR, CBA, C58, and RF, at different levels. We used an H-2Kk-specific monoclonal antibody (mAb) to test the hypothesis that this phenomenon is due to differences in the H-2-restricting element. Initially, we established the specificity of this mAb for the Epa-1-restricting element by demonstrating its capacity to inhibit the lysis of CBA EC by Epa-1-specific CTL. We then used it as the probe in a cellular radioimmunoassay to quantify the expression of the restricting element by EC of different H-2k strains. We found that C58 and RF EC bound significantly less of the mAb than did CBA EC. Although AKR also bound less of the mAb than did CBA EC, the difference was not statistically significant. To examine the generality of this phenomenon, we quantified the expression of Kk antigens on spleen cells (SC) of the same four strains. We found that RF SC, but not AKR or C58 SC, bound significantly less of the Kk mAb than did CBA SC. Thus, the differential CTL lysis of Epa-1+ EC of different strains probably reflects differences in expression of the H-2-restricting element rather than of the nominal antigen.
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    Notes: Phenotypes positive for G2m(23) but negative for Glm(3) and G3m(5,10,11,13,14) are generally very infrequent in Caucasian populations. We recently Gm typed 372 Australian blood donors, predominantly of European descent, and found two Gm(1;23) and five Gm(1,2;23) individuals among them. This finding suggests that the haplotypes Gm1,17:23;21 and Gm1,2,17,23,21 may occur, in some European populations, with a frequency considerably higher than has been generally assumed.
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    Notes: The cosmid H3.5, containing genes mapping to the murine H-2 Qa region, was used to transfect L cells by the calcium phosphate co-precipitation method. The resultant transfected cells expressed a Qa-like determinant as detected by an immune serum raised against the transfectant cells and Qa specific monoclonal antibodies. Two-dimensional gel analysis revealed the expression of a class I-like heavy chain with a similar molecular mass to the Qa2 antigens of the positive strain B10 and B10.A but with a different isoelectric point. The cosmid H3.5 spans 40 kb of DNA and contains at least one complete Qa region gene which encodes the Qa-like determinant detected in this study.
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    Notes: Control by genes within H-2 of natural resistance to fully virulent salmonellae in susceptible mice was studied by the typhoid relapse model. Susceptible (Itys), H-2 congenic C57BL/10 (B10) lines were infected with a lethal dose of the virulent S. typhimurium C5 and rescued from death by ampicillin therapy, inducing a chronic infection. The response to therapy and its cessation, both early and late in the infection, varied in different strains. B10 (H-Zb) and B10.D2 (H-2d) responded less well to therapy, and were more prone to relapse on its removal, than B10.A (H-2a) or B10.M (H-2f) mice. This haplotype distribution is the same as that previously reported for H-2 linked resistance and susceptibility of similar mice to salmonellae of low virulence. The results indicate that resistance to a virulent salmonella capable of causing natural infection is influenced by genes within the MHC.
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    Notes: A case of recombination between the putative class I ELA antigen series and the strudure(s) governing mixed lymphocyte reactivity in an informative horse family is described. The results of serological typing, ‘lysostripping’ and mixed lymphocyte culture tests strongly suggest that the recombination took place between two loci and is not intragenic. An alloantigenic membrane structure, provisionally called B1, which does not belong to the known ELA series, was also involved in the cross-over. The B1 antigen resembles the class II gene products of other species in two respects: it is not present on platelets, and doantiserum with specificity for B1 inhibits the stimulatory effect of B1-carrying cells in mixed lymphocyte cultures. The B1 antigen does not follow the classical distribution, however, being expressed on both B and T lymphocytes. The finding of separate loci for the first series of ELA antigens and the MLR governing structure(s) demonstrates the similarity of the genetic organization of the horse MHC to that in other species.
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    Notes: HLA-A,B,C and DR antigen frequencies were determined in a group of 188 patients suffering from acute myeloid (AML) and acute lymphoid leukaemia (ALL). These antigen frequencies were compared with those obtained on a panel of normal individuals (n= 109) of the same ethnic origin. The significance of the differences in the antigen distribution and the strength of the associations between particular HLA antigens and the disease were then calculated. The resuks obtained show a decreased frequency of HLA-Awl9 in the overall group of patients and the group of patients with ALL. In addition, the antigen frequency of the HLA-B18 and DRS(DRw11) antigens was also decreased in the overall group of patients and in those patients with AML but not in the patients with ALL. The results suggest that the antigen Aw l9 may confer some degree of resistance to the development of ALL and that the HLA-B18 and/or DR5 antigens may be resistance factors for the development of AML.
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    Notes: Ultraviolet tight (UV)-induced tumours in mice are often highly immunogenic and have unique (individually specific) antigens which cause tumour rejection in normal mice. The molecular nature of these unique ‘rejection’ or ‘transplantation’ antigens is not known. We have recently isolated a syngeneic monoclonal antibody (mAb), CP28, that recognizes a unique tumour-specific antigen on the UV-induced regressor tumour 1591-RE. Further analysis revealed that the antibody-recognized antigen represents a novel major histocompatibility complex (MHC) class I molecule. However, the relationship of this molecule to the unique T cell-recognized antigen that causes tumour rejection remained unresolved. In this study we have explored the relationship of the antibody-defined tumour-specific novel class I molecule to the rejection antigen, that we have previously defined with a cytolytic T cell (CTL) clone (‘anti-A’). Two different lines of evidence suggested a close relationship. First, it was found that random subclones of the 1591-RE tumour expressed different levels of the CP28-defined antigen which correlated with the level of lysis by the anti-A CTL clone. Second, the selection of antigen-loss variants using either the anti-A CTL clone or the mAb CP28 resulted in the simultaneous loss of both the CP28 as well as the ‘A’ antigen. This tight correlation strongly suggests a relationship between the antibody-defined and the T cell-defined antigen. However, the role of the antibody-recognized antigen in causing transplantation rejection still needs to be determined.
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    International journal of immunogenetics 13 (1986), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: K36.16 is an AKR H-2k thymoma which expresses an aberrant H-2Dd-like allospecificity, does not have a detectable amount of the H-2Kk syngeneic antigen and grows very easily in syngeneic mice. By DNA-mediated gene transfer experiments, we were able to obtain transformed clones which do express the H-2Kk molecules and are rejected by AKR mice. Southern hybridization was performed to assess whether any gross changes had occurred in the K36.16 H-2K locus or elsewhere in the MHC, which might explain the lack of H-2K expression and/or the presence of the aberrant H-2Dd-like allospecificity. Specific H-2 class I DNA probes were used to compare the K36.16 genomic DNA with normal AKR thymus DNA after digestion with a variety of restriction enzymes. After hybridization with the pH-2IIa probe a 2.8 kb ‘Hind III’ fragment was identified in the K36.16 genomic DNA which is absent from AKR DNA. The pH-2IIa probe detects the third, transmembrane and cytoplasmic domains of class I genes. Although these changes are indicative of MHC genome modifications it is not yet possible to link these specific Southern blot pattern variations with the phenotypic changes mentioned above.
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    Electronic Resource
    Electronic Resource
    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: By means of immunoperoxidase staining of frozen sections 100 primary colorectal carcinomas and 19 metastases were studied for the expression of HLA-A,B,C antigens. A substantial number of the tumours showed a deficient class I expression. The loss of HLA-A,B,C correlated with the degree of de-differentiation.
    Type of Medium: Electronic Resource
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