共查询到20条相似文献,搜索用时 15 毫秒
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Human and mouse major histocompatibility complex class II beta chain alleles associated with predisposition to type I diabetes
often encode a non-charged residue at position 57 rather than the negatively charged aspartate residue characteristic of non-susceptible
haplotypes. The mechanism(s) whereby this polymorphism promotes eventual pancreatic beta cell destruction is unclear. The
type I diabetes-susceptible mouse strain NOD (H2g7) encodes serine at Ab position 57 and is one of the few mouse class II molecules not encoding aspartate at this position.
To gain insight into the structural impact of this amino acid substitution and any influence it may have on T-cell selection,
we assessed whether T-cell repertoires selected by diabetogenic class II (Ag7) are tolerant of mutant Ab (residues 56 and 57) H2-Ag7. We find that NOD mice mount an allogeneic response to skin grafts expressing mutant position 57 (serine to aspartate) Abg7; but not to grafts expressing mutant position 56 (histidine to proline) Abg7. Graft rejection correlates with the presence of CD4+ T cells specific for the mutant H2-Ag7 heterodimer. Genetic analyses are consistent with Ab position 57 aspartate/non-aspartate dimorphism influencing peptide selection
and hence repertoire selection. Direct evidence for the serine to aspartate substitution at position 57 influencing T-cell
selection is found by analysis of peripheral T-cell receptor (TCR) usage and the CD4/CD8 T-cell ratio.
Received: 18 June 1997 / Revised: 18 September 1997 相似文献
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David T. Evans Marian S. Piekarczyk Luis Cadavid Virginia S. Hinshaw D. I. Watkins 《Immunogenetics》1998,47(3):206-211
The products of the highly polymorphic and variable major histocompatibility complex (MHC) class I loci play a crucial role
in host defenses against infectious disease. While similar alleles have been found in closely related species, sharing of
a functional MHC class I allele between two species has never been reported. Here we show that an identical functional MHC
class I molecule is present in two different primate species with an approximate divergence time of 0.7 million years. Lymphocytes
from the red-crested tamarin (Saguinus geoffroyi) expressed an MHC class I allele (Sage-G
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01) that was identical in coding sequence to an MHC class I allele (Saoe-G
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08) found in the cotton-top tamarin (Saguinus oedipus). Furthermore, influenza virus-specific cytotoxic T lymphocytes (CTLs) generated in the cotton-top tamarin killed lymphocytes
expressing the influenza virus nucleoprotein (NP) from the red-crested tamarin. Since the influenza virus NP epitope is bound
by Saoe-G*08 in the cotton-top tamarin, it is likely that this molecule is functional in both species. These data provide the first
evidence that functional MHC class I molecules can be maintained entirely intact in two separate species.
Received: 6 June 1997 / Revised: 21 July 1997 相似文献
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We analyzed the polymorphic nature of eleven alleles expressed by the major class I locus (B-FIV) in chickens. Similar to mammalian class I loci, the nucleotide substitutions with high variability occur in exons 2 and
3 encoding the α1 and α2 domains. However, the nonsynonymous to synonymous ratio of nucleotide substitutions in exon 3 encoding
the α helix and β sheets is reversed compared with HLA. The region of exon 3 encoding the α2 helix demonstrates a much lower
nonsynonymous to synonymous ratio, suggesting evolutionary selection of a more conserved α2 helix in B-FIV compared with HLA.
Amino acid residues with high Wu-Kabat variability are typically located in positions predicted to impact antigen presentation.
B-FIV amino acid residues predicted to interact with the CDR1α region of the T-cell receptor (Tcr) demonstrate less variability
than in mouse and human class I alleles. The combination of a reduced nonsynonymous to synonymous ratio in exon 3 encoding
the α2 helix and the limited variability in CDR1α contact residues is discussed with regard to concerted evolution between
a minimal major histocompatibility complex and compaction of Tcr variable gene segments in the chicken.
Received: 18 Juli 1997 / Revised: 21 November 1997 相似文献
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N. T. Young D. L. Roelen Margaret J. Dallman Peter J. Morris Ken I. Welsh 《Immunogenetics》1998,47(4):310-317
The generation of interleukin-2 (IL-2)-mediated helper activity is a central step in the immune response induced by allogeneic
histocompatibility antigens, and IL-2-producing helper T-lymphocyte precursor (HTLp) frequencies have been proposed as a measure
of alloreactivity in transplant recipients. We analyzed the influence of HLA-matching on the alloresponse of HTLp in limiting
dilution assays derived from healthy individuals. Mean HTLp frequencies were significantly higher in HLA-DR antigen-mismatched
than HLA-DR-matched combinations. Significant differences in the effect of one or two mismatched HLA-DR antigens on mean HTLp
frequencies were also detected. Mean HLA class I (HLA-A, -B, -Cw) mismatches were not significantly different in each group
and had no apparent influence on HTLp frequencies. Analysis of HLA protein sequence disparities revealed no significant difference
in the number of mismatched amino acid residues at the HLA-DRB1 locus between one and two HLA-DR antigen-mismatched combinations
but correlated strongly with HTLp frequency. The positive correlation was evident with mismatched residues in the beta sheet
and alpha helical regions of the HLA-DRB1 molecule, suggesting a predominant influence of bound peptides in the stimulation
of alloreactive helper cells. This finding was supported by analysis of the location of individual residue mismatches. Evidence
of an effect of polymorphism in the CD4-binding region in the β-2 domain of HLA-DRB1 molecules was also found. Our results
demonstrate the major influence of HLA-DR amino acid sequence mismatching on alloreactive HTLp frequencies but also suggest
that additional genetic or environmental influences affect the alloreactive helper T-cell repertoire.
Received: 2 September 1997 / Revised: 29 September 1997 相似文献
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Variation in the number of expressed MHC genes in different cattle class I haplotypes 总被引:8,自引:8,他引:0
Ellis SA Holmes EC Staines KA Smith KB Stear MJ McKeever DJ MacHugh ND Morrison WI 《Immunogenetics》1999,50(5-6):319-328
Analysis of cattle major histocompatibility complex (MHC) (BoLA) class I gene expression using serological and biochemical methods has demonstrated a high level of polymorphism. However,
analysis of class I cDNA sequences has failed to produce conclusive evidence concerning the number and nature of expressed
genes. Such information is essential for detailed studies of cattle immune responses, and to increase our understanding of
the mechanisms of MHC evolution. In this study a selective breeding programme has been used to generate a number of MHC homozygous
cattle expressing common serologically defined class I specificities. Detailed analysis of five class I haplotypes was carried
out, with transcribed class I genes identified and characterized by cDNA cloning, sequence analysis, and transfection/expression
studies. Surface expression of the gene products (on lymphocytes) was confirmed using monoclonal antibodies of defined BoLA specificity. Phylogenetic analysis of available transcribed cattle MHC class I sequences revealed complex evolutionary relationships
including possible evidence for recombination. The study of individual haplotypes suggests that certain groupings of related
sequences may correlate with loci, but overall it was not possible to define the origin of individual alleles using this approach.
The most striking finding of this study is that none of the cattle class I genes is consistently expressed, and that in contrast
to human, haplotypes differ from one another in both the number and composition of expressed classical class I genes.
Received: 15 February 1999 / Revised: 23 June 1999 相似文献
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Lisbeth B. Møller Jim Kaufman Sten Verland Jan Salomonsen David Avila John D. Lambris Karsten Skjødt 《Immunogenetics》1991,34(2):110-120
Molecular variation among major histocompatibility complex (MHC) class I (B-F) proteins from B-homozygous chickens is apparently caused by C-terminal variation. Analysis of the total B-F protein pool revealed substantial heterogeneity with two or three molecular mass constituents, each being comprised by several isoelectric focusing variants. This heterogeneity could not be reduced by enzymatic deglycosylation. By contrast, proteolytic removal of a small (M
r 1000–4000) fragment from the chain resulted in the generation of a M
r 36 000 fragment, common to all the molecular mass variants. Unlike the parent proteins, the M
r 36 000 fragment derived from isolated variants yielded identical, simple patterns in two-dimensional gel electrophoresis and identical finger prints in peptide mapping. This, together with N-terminal amino acid sequencing, as well as comparison of hydrophobicity properties of fragments obtained by gradual proteolytic digestion, indicated that the small peptide responsible for the major B-F heterogeneity was situated in the intracellular, C-terminal part. 相似文献
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Four cDNAs encoding the major histocompatibility complex (MHC) class I α chain were isolated from a channel catfish clonal
B-cell cDNA library. Sequence analysis suggests these cDNAs represent three different MHC class I loci. All cDNAs encoded
conserved residues characteristic of the MHC class I α chain: namely, those involved in peptide binding, salt bridges, disulfide
bond formation, and glycosylation. Southern blot analyses of individual outbred and second-generation gynogenetic fish indicated
the existence of both polygenic and polymorphic loci. Northern blot studies demonstrated that catfish B, T, and macrophage
cell lines transcribed markedly higher levels of class I α and β2-microglobulin (β2m) mRNA than fibroblast cell lines. In addition, immunoprecipitation data showed that a 41 000 M
r glycoprotein (presumably class I α) was associated with β2m on the surface of catfish B cells. This latter finding is the first direct evidence for the cell surface association of
β2m with the MHC class I α chain on teleost cells and supports the notion that functional MHC class I proteins exist in teleosts.
Received: 25 March 1998 / Revised: 28 July 1998 相似文献
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A major histocompatibility complex class I allele shared by two species of chimpanzee 总被引:2,自引:2,他引:0
Stewart Cooper Erin J. Adams R. Spencer Wells Christopher M. Walker P. Parham 《Immunogenetics》1998,47(3):212-217
Little is known regarding the rates at which natural selection can modify or retain antigen presenting alleles at the major
histocompatibility complex (MHC). Discovery of identical [1101 base pairs (bp)] coding regions at the MHC class I C locus in Pan troglodytes and Pan paniscus, chimpanzee species that diverged ∼2.3 million years ago, now indicates that a class I allotype can survive for at least
this period. Remarkable conservation was also reflected in the (1799 bp) introns where a maximum of only six substitutions
distinguished five alleles (three from P. troglodytes and two from P. paniscus) that encoded the identical heavy chain allotype. Analysis of a more distantly related human allele, HLA-Cw
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0702, corroborated that intron variation was non-uniform along the gene. Thus we provide a clear reference frame for the lifetime
of an MHC class I allotype, a direct estimate of allelic substitution rates, and evidence for an unusual evolution of MHC
class I introns.
Received: 13 August 1997 相似文献
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We carried out an analysis of partial sequences from expressed major histocompatibility complex (MHC) class I genes isolated
from a range of equid species and more distantly related members of the mammalian order Perissodactyla. Phylogenetic analysis
revealed a minimum of six groups, five of which contained genes and alleles that are found in equid species and one group
specific to the rhinoceros. Four of the groups contained only one, or very few sequences, indicating the presence of relatively
nonpolymorphic loci, while another group contained the majority of the equid sequences identified. These data suggest that
a diversification of MHC genes took place after the split between the Equidae and the Rhinocerotidae yet before the speciation
events within the genus Equus.
Received: 17 November 1998 / Accepted: 7 April 1999 相似文献
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A. B. Geldhof Thierry VandenDriessche Ghislain Opdenakker Patrick De Baetselier 《Cancer immunology, immunotherapy : CII》1996,42(6):329-338
Interferon-γ(IFNγ)-induced up-regulation of MHC class I expression on tumor cells can induce a potent CD8-mediated antitumor
response. Consequently, many investigators have proposed IFNγ gene transfection as a means to immunogenize tumor cells and
to vaccinate against metastatic disease. In this study, we demonstrate that transfection of the IFNγ gene in a BW5147 variant
(LiDlo) with low MHC class I expression results in a selective induction of H-2Dk but unaltered H-2Kk expression. In earlier reports we demonstrated a positive correlation between H-2Dk expression and enhanced metastatic potential of BW variants. In accordance with these observations, we observed that intravenous
inoculation of LiDlo(IFNγ) variants into syngeneic AKR mice led to enhanced metastasis as compared to parental LiDlo and LiDlo(neo) control transfectants. Tumor cells, derived from local subcutaneous tumors or sporadic metastases from mice inoculated
with LiDlo tumor cells, were found to up-regulate H-2Dk selectively. Anti-asialoGM1 treatment of AKR mice allowed rapid experimental metastasis formation by the LiDlo and LiDlo(neo) variants, indicating that natural killer (NK) cells control the metastatic behavior of these tumor cells. This was corroborated
by in vitro cytotoxicity experiments, demonstrating that LiDlo and LiDlo(neo) tumor cells were NK-sensitive, while the BW IFNγ transfectants became resistant to lymphokine-activated killer cells
and poly(I)·poly(C)-induced NK cells. We thus conclude that (a) IFNγ up-regulates selectively the MHC class I antigen H-2Dk, (b) H-2Dk governs susceptibility towards NK cells, and (c) NK susceptibility determines the experimental metastatic behavior of BW
tumor cells.
Received: 2 May 1996/Accepted: 21 May 1996 相似文献