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  • Articles  (18)
  • MHC  (18)
  • Springer  (18)
  • American Institute of Physics (AIP)
  • Oxford University Press
  • Wiley
  • 1995-1999  (18)
  • 1999  (18)
  • Medicine  (18)
  • Physics
Collection
  • Articles  (18)
Source
Keywords
Publisher
  • Springer  (18)
  • American Institute of Physics (AIP)
  • Oxford University Press
  • Wiley
Years
  • 1995-1999  (18)
Year
Topic
  • 1
    Electronic Resource
    Electronic Resource
    Absence of MHC class II gene expression in a patient with a single amino acid substitution in the class II transactivator protein CIITA (1999)
    Springer
    Immunogenetics 49 (1999), S. 957-963 
    Details
    ISSN: 1432-1211
    Keywords: Key words CIITA ; MHC ; Class II ; Bare lymphocyte syndrome ; Transcription
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  We investigated the underlying genetic defect in an immunodeficient patient who presented with recurrent bacterial infections in his late twenties and demonstrated a transcriptional defect in major histocompatibility complex (MHC) class II regulation. Transient heterokaryon analysis implicated functional loss of CIITA, the MHC class II transactivator protein, and in support of this MHC class II antigen expression was restored by stable transfection with the wild-type molecule. A single amino acid substitution, phenylalanine to serine, in the COOH-terminal portion of the CIITA sequence correlated with reduced transcription of both classical (HLA-DP, -DQ, and -DR) and nonclassical (HLA-DM and –DO) class II genes. The long survival of the patient, although remarkable, was not associated with partial CIITA function as evidenced by residual MHC class II expression. These data define at high resolution a region of CIITA that is essential for function in both professional and nonprofessional antigen presenting cells and which could potentially constitute a target for therapeutic intervention by novel factors with a propensity to downregulate MHC class II antigen expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050579
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  • 2
    Electronic Resource
    Electronic Resource
    The central MHC gene IKBL carries a structural polymorphism that is associated with HLA-A3,B7,DR15 (1999)
    Springer
    Immunogenetics 49 (1999), S. 660-665 
    Details
    ISSN: 1432-1211
    Keywords: Key words IKBL ; MHC ; TNF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Susceptibility to several disorders, including insulin-dependent diabetes mellitus and multiple sclerosis, has been associated with alleles of HLA class II genes and loci in the TNF cluster in the central major histocompatibility complex (MHC) region. As recombination within this region is rare, it is difficult to determine which genes are important. This will be facilitated by the identification of functional polymorphisms. Hence we are sequencing reverse transcription-polymerase chain reaction products derived from central MHC genes in well characterized and conserved ancestral haplotypes. Here we address the IKBL gene, which lies near the TNF cluster at the telomeric end of the central MHC. Although the IKBL cDNA sequence was conserved between most ancestral haplotypes, a synonymous nucleotide substitution, a 3' untranslated region substitution, and a single nonsynonymous substitution were identified. The latter (IKBL+738) was present in multiple examples of the 7.1 haplotype [HLA-A3, B7, DR2 (DR15)] and resulted in a cysteine to arginine substitution in a predicted protein kinase C phosphorylation site. This polymorphism did not occur in 18 other common haplotypes from the 10th International Histocompatibility Workshop and thus appears haplospecific. A role for IKBL+738 in the association between HLA-A3,B7,DR2(DR15) and susceptibility to multiple sclerosis is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050662
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  • 3
    Electronic Resource
    Electronic Resource
    Gene conversion of major histocompatibility complex genes is associated with CpG-rich regions (1999)
    Springer
    Immunogenetics 49 (1999), S. 446-455 
    Details
    ISSN: 1432-1211
    Keywords: Key words Gene conversion ; MHC ; H2 ; HLA ; CpG ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  We examined 32 DNA sequences of mouse and human major histocompatibility complex (MHC) genes believed to have been subjected to gene conversion events. All regions of the mouse H2 genes as well as the human HLA genes which have been implied to be involved in gene conversion events had elevated levels of CpG dinucleotides, whereas the rest of the genes showed extensive CpG suppression. Mouse MHC genes which have been suspected but not directly implied to be involved in gene conversion events also showed elevated levels of CpG dinucleotides. Moreover, both mouse and human MHC genes which have never been suspected of undergoing gene conversion had low levels of CpG throughout the genes. These results indicate that high CpG levels are correlated with gene conversion rather than with polymorphism, as non-polymorphic genes that have been implicated as gene conversion donors also have elevated levels of CpG dimers in the involved regions, whereas polymorphic genes which have never been considered to undergo gene conversion events have a low level of CpG dinucleotides. We also studied the methylation pattern of CpG dimers in the Abk gene by restriction enzyme digestion of mouse testis DNA followed by Southern blot and hybridization to an Abk-specific probe. The examined CpG dimers in prepubescent mice, where the latest germline stages are spermatogonia, leptene, or pachytene, are respectively non-methylated. Accordingly, the CpG dimers appear to be non-methylated in germline DNA from the testis of prepubescent mice, where gene conversions have been reported to occur.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050518
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  • 4
    Electronic Resource
    Electronic Resource
    The sequence and organization of the mouse valyl-tRNA synthetase gene G7a/Bat6 located in the MHC class III region (1999)
    Springer
    Immunogenetics 49 (1999), S. 468-470 
    Details
    ISSN: 1432-1211
    Keywords: Key words Mouse ; MHC ; Class III ; G7a/Bat6/D17H6S56E ; Valyl-tRNA synthetase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050522
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  • 5
    Electronic Resource
    Electronic Resource
    Mapping of a candidate region for susceptibility to inclusion body myositis in the human major histocompatibility complex (1999)
    Springer
    Immunogenetics 49 (1999), S. 508-516 
    Details
    ISSN: 1432-1211
    Keywords: Key words Inclusion body myositis ; Ancestral haplotypes ; MHC ; HSP70 ; TNF ; Microsatellites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Inclusion body myositis (IBM) is a form of idiopathic inflammatory myopathy of unknown aetiology. A strong association with HLA class II (HLA-DR3) suggested a role for genes in the human major histocompatibility complex (MHC) in the predisposition to this disease. In this study, we have taken advantage of the ancestral haplotype (AH) concept and historical recombinations to map for a possible susceptibility gene(s) in the MHC. We performed detailed typing of three MHC-related HSP70 genes and defined allelic combinations in the context of MHC AH. We also modified existing methods to give a simple and accurate method for typing two TNF microsatellites. Using the HSP70 and TNF markers and HLA-DR, –B, and C4 typing of our patients with IBM, we defined a potential site for the MHC-associated susceptibility gene(s) in the region between HLA-DR and C4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050528
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  • 6
    Electronic Resource
    Electronic Resource
    Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism (1999)
    Springer
    Immunogenetics 50 (1999), S. 201-212 
    Details
    ISSN: 1432-1211
    Keywords: Key words Vaccines ; Epitopes ; HLA ; Supertypes ; Polymorphism ; MHC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Herein, we review the epitope approach to vaccine development, and discuss how knowledge of HLA supertypes might be used as a tool in the development of such vaccines. After reviewing the main structural features of the A2-, A3-, B7-, and B44- supertype alleles, and biological data demonstrating their immunological relevance, we analyze the frequency at which these supertype alleles are expressed in various ethnicities and discuss the relevance of those observations to vaccine development. Next, the existence of five new supertypes (A1, A24, B27, B58, and B62) is reported. As a result, it is possible to account for the predominance of all known HLA class I with only nine main functional binding specificities. The practical implications of this finding, as well as its relevance to understanding the functional implication of MHC polymorphism in humans, are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050594
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  • 7
    Electronic Resource
    Electronic Resource
    In vivo analysis of HLA-DQ gene expression in heterozygous cell lines (1999)
    Springer
    Immunogenetics 50 (1999), S. 309-318 
    Details
    ISSN: 1432-1211
    Keywords: Key words Human ; B lymphocytes ; Gene regulation ; MHC ; mRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Regulation of HLA-DQ gene transcription is a complex phenomenon because the allelic polymorphism associated with these genes and their promoters is a putative source of differential allele expression. Both transcriptional and post-transcriptional regulation could account for the density of the molecules expressed at the cell surface and then for the specificity of the immune response. Different methods have been developed to evaluate the functional consequences of this polymorphism, but at present no universal method allows measurement of either the steady-state level or the half-life time of mRNA species of both DQA1 and DQB1 polymorphic genes in heterozygous cell lines. Here, we propose a potent method, based on relative quantification of reverse transcriptase-polymerase chain reaction products, which analyzes the differential expression of all DQA1 or DQB1 allele combinations. This method is used to analyze the differential expression of HLA-DQB1*0201/0402 alleles in the human heterozygous lymphoblastoid B-cell line. Nucleotidic sequences of the proximal upstream regulatory region of these alleles exhibit significant differences. We show that the DQB1*0402 promoter is able to mediate a transcription strength twice as efficiently as *0201. In addition, the *0402 mRNA steady-state level is also governed by a remarkable post-transcriptional regulation. Indeed, an important part (20%) of the *0402 primary transcript is derived by alternative splicing in a short mRNA translated into a nonfunctional protein. Despite their variable sequence and length, no difference in the half-life of DQB1*0201 and both DQB*0402 mRNAs was observed in B-lymphoblastoid cells. The implications of these findings are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050607
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  • 8
    Electronic Resource
    Electronic Resource
    Characterization of the mouse proteasome regulator PA28b gene (1999)
    Springer
    Immunogenetics 49 (1999), S. 149-157 
    Details
    ISSN: 1432-1211
    Keywords: Key words Proteasome ; PA28 ; IFN ; MHC ; Class I
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The proteasome regulator PA28, which can be upregulated by IFN, is important in the modulation of proteasome activity. Since the proteasome has been implicated in the processing of the major histocompatibility complex (MHC) class I antigens, it was of interest to determine the regulatory elements of PA28 at the genomic level. Although PA28 has been found in different species, the gene layout on the chromosome was not determined. In this study, the genetic organization of mouse PA28b was characterized. Two copies of the PA28b gene, namely b1 and b2, were found by restriction fragment mapping and Southern hybridization. By fluorescence in situ hybridization, the location of the two PA28b genes was determined on chromosomes 11 and 14. PA28b1 has 11 exons, whereas PA28b2 has no introns and appears to be a nonfunctional pseudogene. The 5' promoter region of PA28b1 contains several transcriptional factor binding sites including two IFN responsive elements. The expression levels of PA28 and other gene products involved in MHC class I antigen presentation appear to be correlated in various tissues. Notably, PA28 is expressed at high levels in immunological tissues such as spleen and peripheral blood leukocytes. Taken together, PA28 seems to be co-regulated with other molecules involved in MHC class I antigen presentation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050476
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  • 9
    Electronic Resource
    Electronic Resource
    Complete cDNA sequences of the DRB6 gene from humans and chimpanzees: a possible model of a stop codon readingthrough mechanism in primates (1999)
    Springer
    Immunogenetics 49 (1999), S. 843-850 
    Details
    ISSN: 1432-1211
    Keywords: Key words DRB6 ; MHC ; Primates ; Readingthrough mechanism ; Selenocysteine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The defective major histocompatibility complex (MHC) DRB6 gene is transcribed into mRNA in human [peripheral blood lymphocytes, transfected and Epstein-Barr virus (EBV)] and chimpanzee EBV cell lines. MHC-DRB6 presents several anomalies, which include stop codons in exon 2, lack of the usual polyadenilation signal of other MHC-DRB genes, and a promoter region and exon 1 taken from a locally inserted retrovirus. The complete cDNA sequences from human DRB6*0201 and three common chimpanzee alleles (Patr-DRB6*0108, Patr-DRB6*0109, Patr-DRB6*0111) have been obtained; two exon 1-exon 2 cDNA sequences from bonobos (Papa-DRB6*0101 and Papa-DRB6*0102) are also shown. In contrast to chimpanzee DRB6 transcripts, the human ones: (1) present an exon 1-exon 2 splicing site that includes the transcription of the first 141 nucleotides of intron 1, rendering a longer exon 1, and (2) show a duplication of exon 6, which would render a longer cytoplasmic tail in a putative DRB6 protein. These two characteristics are found in all the human sequences obtained, regardless of the cellular type tested, and they are not present in any of the chimpanzee alleles reported; consequently, they are human-specific. All the alleles reported here bear stop codons in the three possible reading frames; however, a certain level of expression of DRB6 has been observed by cytofluorometry. This could be due to the presence of a selenocysteine insertion sequence (SECIS) stem-loop structure located at the 3 untranslated region of the DRB6 mRNA, which directs selenocysteine incorporation at UGA codons. DRB6 transcription and translation would be the first gene model of a readingthrough stop codon mechanism in primate MHC. It is also feasible that the DRB6 gene might generate a population of short polypeptides, bound to plasmatic membranes, having non-antigen-presenting functions or which are presented by other MHC molecules as HLA-E presents HLA-G and -B leader sequence-derived peptides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050563
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  • 10
    Electronic Resource
    Electronic Resource
    Antigen presentation in Syrian hamster cells: substrate selectivity of TAP controlled by polymorphic residues in TAP1 and differential requirements for loading of H2 class I molecules (1999)
    Springer
    Immunogenetics 49 (1999), S. 931-941 
    Details
    ISSN: 1432-1211
    Keywords: Key words Syrian Hamster ; MHC ; Antigen presentation ; Peptide transporters (TAP)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Expression of mouse major histocompatibility complex (MHC) class I molecules in different cell lines derived from Syrian hamsters has revealed antigen presentation deficiencies of some H2 allelic products in two cell lines (BHK and NIL-2) which were overcome by transient expression of the rat transporter associated with antigen processing (TAP; Lobigs et al. 1995). Here we show that in both cell lines the endogenous MHC class I cell surface expression was completely down-regulated. Lymphokine treatment induced endogenous and recombinant mouse MHC class I cell surface expression to levels similar to that in other Syrian hamster cell lines competent for antigen presentation through transduced H2 molecules. Accordingly, constitutive downregulation of expression of accessory molecules of the MHC class I pathway can reveal differences between H2 class I alleles in antigen presentation not encountered when the expression levels are augmented. In addition to the differential expression of MHC class I pathway genes, two cell lines representing competent (FF) and defective (BHK) antigen presentation phenotypes for mouse class I MHC restriction elements demonstrated substantial sequence polymorphism in Tap1 but not Tap2. Cytokine-treated FF or BHK cells and human TAP-deficient T2 cells transfected with FF or BHK TAP1 in combination with FF TAP2 differed in their preference for C-terminal peptide residues, as shown by an in vitro peptide transport assay. Thus, polymorphic residues in TAP1 can influence the substrate selectivity of the Syrian hamster peptide transporter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050576
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  • 11
    Electronic Resource
    Electronic Resource
    Isolation of transporter associated with antigen processing genes, TAP1 and TAP2, from the horned shark Heterodontus francisci (1999)
    Springer
    Immunogenetics 49 (1999), S. 981-986 
    Details
    ISSN: 1432-1211
    Keywords: Key words Transporter ; Shark ; MHC ; cDNA sequence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050582
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  • 12
    Electronic Resource
    Electronic Resource
    Co-evolving genes in MHC haplotypes: the "rule" for nonmammalian vertebrates? (1999)
    Springer
    Immunogenetics 50 (1999), S. 228-236 
    Details
    ISSN: 1432-1211
    Keywords: Key words Co-evolution ; MHC ; Vertebrate ; Genome ; TAP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050597
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  • 13
    Electronic Resource
    Electronic Resource
    Peptide motif of HLA-B*1510 (1999)
    Springer
    Immunogenetics 49 (1999), S. 996-999 
    Details
    ISSN: 1432-1211
    Keywords: Key words Peptide motif ; HLA-B*1510 ; Pockets ; Anchor ; MHC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050585
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  • 14
    Electronic Resource
    Electronic Resource
    MHC class I genes in a New World primate, the cotton-top tamarin (Saguinus oedipus), have evolved by an active process of loci turnover (1999)
    Springer
    Immunogenetics 49 (1999), S. 196-205 
    Details
    ISSN: 1432-1211
    Keywords: Key words New world primates ; MHC ; Evolution ; Gene duplication
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Lymphocytes of a New World primate, the cotton-top tamarin (Saguinus oedipus), express classical G–related major histocompatibility complex (MHC) class I molecules with unusually limited polymorphism and variability. Three G-related loci, an F locus, an E locus, and two pseudogenes (So-N1 and So-N3) have been identified by cDNA library screening and extensive PCR analysis of both cDNA and genomic DNA from the cotton-top tamarin. Furthermore, each genus of the subfamily Callitrichinae (tamarins and marmosets) appears to express its own unique set of MHC class I genes, likely due to a rapid turnover of loci. The rapid emergence of unique MHC class I genes in the Callitrichinae genera, resulting from an active process of duplication and inactivation of loci, may account for the limited diversity of the MHC class I genes in the cotton-top tamarin. To determine the nature of the entire complement of MHC class I genes in the cotton-top tamarin, we synthesized a genomic DNA library and screened it with MHC class I-specific probes. We isolated nine new MHC class I pseudogenes from this library. These newly isolated tamarin G–related MHC class I pseudogenes are not closely related to any of their functional counterparts in the tamarin, suggesting that they do not share a recent common ancestral gene with the tamarin's currently expressed MHC class I loci. In addition, these tamarin sequences display a high rate of nonsynonymous substitutions in their putative peptide binding region. This indicates that the genes from which they have derived were likely subject to positive selection and, therefore, were once functional. Our data support the notion that an extremely high rate of loci turnover is largely responsible for the limited diversity of the MHC class I genes in the cotton-top tamarin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050480
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  • 15
    Electronic Resource
    Electronic Resource
    Detection of polymorphism in the RING3 gene by high-throughput fluorescent SSCP analysis (1999)
    Springer
    Immunogenetics 49 (1999), S. 256-265 
    Details
    ISSN: 1432-1211
    Keywords: Key words RING3 ; SSCP ; HLA ; MHC ; Polymorphism ; Leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  We describe the use of a high-throughput, fluorescent, polymorphism-detection system, based on single-strand conformation polymorphism to screen for polymorphism in the RING3 gene. This is the first extensive mutation screen of this major histocompatibility complex-linked gene, and the entire coding region and intron-exon junctions were examined by multiplexing over 3000 polymerase chain reaction products. These techniques should be applicable for analysis of variation in other human genes. Investigation of DNA from acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) patients, as well as healthy individuals revealed low levels of polymorphism across the RING3 gene. Comparison of the distribution of genotypes at each polymorphic site between patients and healthy individuals revealed a single site which significantly deviates from Hardy-Weinberg proportions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050491
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  • 16
    Electronic Resource
    Electronic Resource
    MICA haplotypic diversity (1999)
    Springer
    Immunogenetics 49 (1999), S. 557-560 
    Details
    ISSN: 1432-1211
    Keywords: Key words MICA ; HLA ; MHC ; Haplotypes ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050536
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  • 17
    Electronic Resource
    Electronic Resource
    The HLA-A*6601 peptide motif: prediction by pocket structure and verification by peptide analysis (1999)
    Springer
    Immunogenetics 49 (1999), S. 571-576 
    Details
    ISSN: 1432-1211
    Keywords: Key words HLA-A*6601 ; Peptide motif ; Pockets ; MHC ; Anchors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050539
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  • 18
    Electronic Resource
    Electronic Resource
    Selection in favor of the Ped fast haplotype occurs between mid-gestation and birth (1999)
    Springer
    Immunogenetics 49 (1999), S. 653-659 
    Details
    ISSN: 1432-1211
    Keywords: Key words Ped ; Preimplantation ; Embryo ; MHC ; Class Ib
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The preimplantation embryo development (Ped) gene that encodes the class Ib major histocompatibility complex protein Qa-2 influences the rate of embryonic cleavage during the preimplantation stages of development. Embryos from strains of mice that lack the Ped gene cleave slowly, while embryos that have a functional Ped gene cleave more rapidly. This effect is observed both in vivo and in vitro with the Ped fast haplotype showing dominance over the Ped slow haplotype. The Ped gene is associated with pleiotropic effects on reproduction. Certain strains of mice lacking the Ped gene (Ped slow) have smaller litters and the pups weigh less at birth and at weaning. Previously our laboratory reported that in litters derived from Ped fast/slow F1 mice backcrossed to the slow/slow parent, there were significantly more Ped fast pups than the 50% expected, at two months of age. This implies that there is selection in favor of the Ped fast haplotype at some point during development. The present study was designed to determine at what point during development selection occurs. Using a polymerase chain reaction assay, we determined that selection does not occur by days post coitus 14.5. However, our results show that there are significantly more Ped fast pups than Ped slow pups remaining in backcross litters just after birth, indicating that selection in favor of the Ped fast haplotype occurs between day 14.5 and birth.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050661
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