SEARCH · PubMed Health

Results for “Major Histocompatibility Complex”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1978

Major histocompatibility complex and non-major histocompatibility complex antigens on mouse ectoplacental cone and placental trophoblastic cells.

The expression of major histocompatibility complex and non-major histocompatibility complex antigens on mouse trophoblast cultured from two defined stages of development was investigated by the sensitive in vitro mixed haemadsorption assay. Outgrowths obtained 3 to 5 days after explanation of 7 1/2-day ectoplacental cones contained a mixed population of cells. Those with a giant cell morphology showed no haemadsorption with congenic H-2 antisera and were reactive with non H-2 antiserum only in the CBA strain. Other, smaller cells were reactive for both H-2 and non-H-2 in all strains examined except for C57BL, where the cells were nonreactive for H-2. Monolayer cultures of 13 to 14-day placental suspensions tested 24 hr after preparation were strongly reactive for both H-2 and non-H-2. The identity and alloantigenic status of the cells are discussed in relation to their function in maternal-foetal immunological interactions.

Animals↗

PubMed1991

Evolution of the major histocompatibility complex: molecular cloning of major histocompatibility complex class I from the amphibian Xenopus.

Class I major histocompatibility complex (MHC) cDNA clones have been isolated from an expression library derived from mRNA of an MHC homozygous Xenopus laevis. The nucleotide and predicted amino acid sequences show definite similarity to MHC class I molecules of higher vertebrates. The immunoglobulin-like alpha-3 domain is more similar to the immunoglobulin-like domains of mammalian class II beta chains than to those of mammalian class I molecules, and a tree based on nucleotide sequences of representative MHC genes is presented.

Amino Acid Sequence↗

PubMedDate not supplied

Complexity in the major histocompatibility complex.

The human major histocompatibility complex (MHC) is one of the most intensively studied regions of the human genome, containing over 70 known genes and spanning about 4 million base pairs (4 Mbp) of DNA on chromosome 6p21.3 (Klein, 1986). It can be divided up into three regions: the class I region (telomeric), the class II region (centromeric), and the class III region (between class I and II), which includes the complement component genes C2, C4, and Bf (Trowsdale & Campbell, 1988). The MHC has been mapped in detail using pulse field gel electrophoresis (PFGE) and by cloning in yeast artificial chromosome (YAC) and cosmid vectors, revealing long stretches of DNA between the regions as well as between individual class I and class II genes. Novel genes, that have no sequence relationships with class I, class II or complement components, have recently been found in these areas, and we will present an update on these after reviewing the more established loci.

Chromosome Mapping↗

PubMed1978

The unity of genes in the major histocompatibility complex.

The major histocompatibility complex (MHC) of the mouse can be genetically divided into several regions specialized to performing specific functions. Thus the class I regions (K and D) code for antigens that activate effector (killer) T cells, class II region (I) for antigens causing T-cell proliferation, and class III regions (s) for complement components. A strong case is made for the theory that the division of labor within the MHC is not absolute. Evidence is presented that class I antigens can sometimes cause as strong T-cell proliferation as class II antigens; that class II antigens can generate effector T cells; and that class I antigens may be involved in the immune response to some antigens. The fact that different regions can perform similar functions argues for the unity of the MHC genes.

Animals↗

PubMed1992

Genes, genes and more genes in the human major histocompatibility complex.

The human major histocompatibility complex (MHC), on the short arm of chromosome 6, represents one of the most extensively characterised regions of the human genome. This approximately 4 Mb segment of DNA contains genes encoding the polymorphic MHC class I and class II molecules which are involved in antigen presentation during an immune response. Recently the whole of the MHC has been cloned in cosmids and/or yeast artificial chromosomes (YACs) and large portions have been characterised for the presence of novel genes. Many unrelated genes, both housekeeping and tissue specific, have been identified and the gene density in some regions is now approaching one gene every few kilobases. Some of the novel genes encode proteins involved in the intracellular processing and transport of antigens that are presented by MHC class I molecules. Others, however, have no obvious role in the immune response. The MHC is located in the chromosome band 6p21.3 which is a Giemsa (G)-light band. The detection of such a large number of functional genes (at least 70) in this region is compatible with the idea that both housekeeping and tissue-specific genes are localised predominantly in G-light bands.

Chromosome Mapping↗

PubMed1991

A first-order reaction controls the binding of antigenic peptides to major histocompatibility complex class II molecules.

Major histocompatibility complex class II molecules have been reported to bind antigenic peptides very slowly in vitro. To investigate the molecular events that govern the slow binding reaction, we have determined the dependence of complex formation and dissociation on peptide concentration. The complex between the purified major histocompatibility complex class II protein I-Ek and a fluoresceinated peptide representing amino acids 89-104 of pigeon cytochrome c (FpCytc) was studied. Two important results emerge from this study. (i) At pH 5.4, the half-time for I-Ek-FpCytc complex formation is equal to approximately 7 hr for peptide concentrations that vary over a range of three orders of magnitude. There is in fact a small but significant decrease in the half-time for complex formation at low peptide concentrations. The small decrease in half-time is related to the release of endogenous peptides. (ii) At large ratios of peptide to protein [( FpCytc]/[I-Ek] greater than 40), the half-times for I-Ek-FpCytc complex formation and dissociation are equal to one another to within a factor of two between pH 7.5 and 4.5. The percent results demonstrate that a slow, first-order reaction precedes complex formation between I-Ek and FpCytc. This first-order reaction may involve a protein conformational change in addition to the release of endogenous peptides.

Antigens↗

PubMed1992

The alpha chain gene of H-2O has an unexpected location in the major histocompatibility complex.

A previously unknown major histocompatibility complex class II molecule consisting of the beta chain encoded by the H-2Ob gene and an unknown alpha chain was recently described. We now report that the alpha chain occurs in two allelic forms distinguished by charge difference. Using inbred recombinant mouse strains we were able to map the H-2Oa gene to a location between the A.TL and B10.MBR recombination points. Cosmids covering this region were used to isolate the gene. Sequence analysis revealed that the H-2Oa gene is the murine equivalent of the human HLA-DNA gene. These results indicate that the human HLA-DNA gene, the existence of which has long been known, is indeed coding for DO alpha, the alpha chain pairing with DO beta.

Amino Acid Sequence↗

PubMed1979

Suppressor T-cell mechanisms in contact sensitivity. III. Apparent non-major histocompatibility complex restriction is a result of multiple sets of major histocompatibility complex-specific suppressor T cells induced by syngeneic 2,4-dinitrophenyl-modified lymphoid cells.

This report has examined the mechanisms by which major histocompatibility complex (MHC) non-restricted suppressor T cells (Ts), induced by the i.v. injection of 2,4-dinitropheny (DNP)-modified, syngeneic lymphoid cells (DNP-LC), suppress the passive transfer of contact sensitivity mediated by syngeneic and allogeneic immune delayed hypersensitivity T cells (TDH). In terms of suppression of syngeneic TDH, it was found that the suppressive action of the Ts was only blocked by pretreatment with soluble syngeneic DNP-LC membrane preparations. Monomeric DNP-lysine, polymeric DNP-protein conjugates, and syngeneic TNP-LC membranes did not inhibit Ts function. Further experiments showed that inhibition of syngeneic suppression could be achieved by DNP-modified-membrane preparations that were only H-2D-region compatible with the Ts donor. Thus, Ts antigen receptors in this system specifically recognize DNP-modified H-2D-region determinants. In contrast, it was found that pretreatment os syninduced Ts with syngeneic DNP-LC membranes did not inhibit the ability to suppress allogeneic TDH. However, pretreatment of Ts with DNP-allogeneic membranes which were H-2D-end compatible to the allogeneic target TDH eliminated their ability to suppress the specific allogeneic TDH, leaving intact suppression of syngeneic or third party TDH. It is proposed that perturbation of the immune system by i.v. injection of syngeneic NDP-LC leads to the induction of a polyclonal wave of DNP-specific Ts activity. Some members of this set of Ts recognize DNP-self MHC determinants with moderate affinity and are thus specifically inhibited after pretreatment with those DNP-self determinants. Other members of this set display receptors which cross-react with high affinity with DNP-allogeneic determinants and thus suppress allogeneic TDH cells. These allosuppressive clones can thus be specifically inhibited only by pretreatment with DNP-LC membranes, MHC-compatible with the target TDH. The data are discussed in terms of current models of T-cell cross-reactivity and T-cell-receptor recognition.

Animals↗

PubMed1976

The evolution of genes in the major histocompatibility complex.

The mammalian major histocompatibility system (MHS) includes genes determining the structure of the classical major transplantation antigens (H-2K and H-2D), the I region-associated (Ia) antigens, and genes determining the structure level or both of the first four components of complement. In addition, the I region incudes a series of genes determining specific immune responsiveness to a wide variety of antigens - the Ir genes. The available evidence indicates that the K, D, and I gene products are cell surface glycoproteins that are structurally and perhaps functionally related. The multiple genes in this complex region apparently arose by a process of tandem gene duplication. There is some reason to believe that the murine MHS may have originated from genes in the T/t complex - a "supergene" near the centromere of the 17th mouse chromosome determining a series of steps in early embryonic development. Other evidence has led to the postulate that genes in the MHS have given rise to immunoglobulin structural genes by a process of translocation and further gene duplication. While these evolutionary relationships are speculative, it seems clear that the MHS determines a series of cell surface proteins that are intimately involved in cellular recognition and interaction, and in regulation of immune responsiveness by a new, nonimmunoglobulin recognition system.

Alleles↗

PubMed2026

Functional Annotation of the Major Histocompatibility Complex Locus.

The human major histocompatibility complex (MHC) locus has the greatest density of disease-associations in the human genome, including links to over 100 polygenic disorders. Its complex haplotype structure, rich gene density, and high degree of linkage disequilibrium combine to make deciphering the gene regulatory logic of the MHC locus extremely challenging. Employing complementary high-throughput CRISPR interference (CRISPRi) and activation (CRISPRa) epigenetic screens coupled with single-cell transcriptome profiling across three distinct human cell types, we identified hundreds of new connections between cis -regulatory elements (CREs) and their target genes in this locus. These CRE-gene links are largely cell type-specific and act as enhancers. Additionally, some CREs have complex features, including harboring both active and repressive histone marks, lacking chromatin accessibility, targeting multiple genes, or acting as silencers. Computational methods fail to predict a majority of these CRE-gene connections. These findings emphasize the potential for functional perturbation experiments to dissect complex loci and reveal shared and cell type-specific regulatory mechanisms relevant to genomics of complex diseases. Collectively, this study provides a unique resource for understanding the complex regulatory landscape within the MHC locus and supports the need for creating new models that encompass CRE-gene interactions, cell type-specific gene expression, and disease genetics in the noncoding genome.

Journal Article↗

PubMed1991

Adenovirus infection inhibits the phosphorylation of major histocompatibility complex class I proteins.

Major histocompatibility complex (MHC) class I molecules act as peptide receptors to direct the recognition of foreign antigens by cytolytic T cells. The cell surface expression and trafficking of these peptide receptors is thought to be controlled by the conformation of the MHC molecule and possibly by the phosphorylation of the cytoplasmic portion of the heavy chain protein. It is of some interest that adenoviruses (Ads) have evolved proteins that interfere with the expression of MHC molecules. One of these proteins, called E3/19k, binds to newly synthesized MHC molecules in the rough endoplasmic reticulum (RER) and inhibits their trafficking to the cell surface. Here we show that during the infection of a human cell line with Ad2, the phosphorylation of the endogenous MHC molecules is inhibited. We also observe that the phosphorylation of the endogenous HLA molecules is grossly impaired in a human cell line transfected with the Ad2 EcoRI D fragment containing the E3/19k gene. We conclude that the E3/19k protein inhibits the phosphorylation of the MHC heavy chains and that this may be one of the important functions of this protein in infected cells. In addition, we show that a mutant of the E3/19k protein, which lacks an RER retention signal but which retains its ability to bind to HLA molecules, does not inhibit the phosphorylation of HLA molecules and that phosphorylated molecules are not Endo H sensitive. This suggests that HLA molecules are phosphorylated after leaving the medial-Golgi compartment, thus providing the most compelling evidence yet that HLA molecules are phosphorylated at or near the cell surface. Finally, to our knowledge, this is the first study under which the phosphorylation of MHC molecules is shown to be altered and may have some relevance for other pathogenic conditions.

Adenoviridae Infections↗

PubMed1992

In vivo function of regulatory DNA sequence elements of a major histocompatibility complex class I gene.

Major histocompatibility complex class I genes are expressed in nearly all somatic tissues, although their level of expression varies. By analysis of a set of promoter deletion mutants introduced into transgenic mice, a complex regulatory element, consisting of overlapping enhancer and silencer activities, is demonstrated to function as a tissue-specific regulator of class I expression. The enhancer activity predominates in lymphoid tissues but not in nonlymphoid tissues. In contrast to the tissue-specific functions of the complex regulatory element, a second novel silencer element is shown to function in both lymphoid and nonlymphoid tissues. The complement of DNA-binding factors in different cell lines is shown to correlate with the levels of class I expression.

Animals↗

PubMed1992

Major histocompatibility complex class I restriction fragment length polymorphism analysis in highly inbred chicken lines and lines selected for major histocompatibility complex and immunoglobulin production.

Selected chicken populations were analyzed by restriction fragment length polymorphism (RFLP) with a chicken MHC Class I (B-F) cDNA probe. The 13 highly inbred chicken lines differed in genetic origin and in MHC (B) haplotype, as distinguished by using hemagglutination with antisera against B-G and B-F antigens. The S1 sublines differed for B haplotype and antibody response to a synthetic polypeptide, GAT. In the highly inbred lines, band-sharing between lines from different origins was less than that between lines from same origin, showing the influence of the genetic background on chicken MHC Class I gene RFLP. In the S1 line, use of three restriction endonucleases (BglII, PvuII, and TaqI) produced MHC Class I RFLP patterns that were associated with B haplotype, but not with immune response to GAT (IrGAT). A previous study in the authors' laboratory also demonstrated an association of MHC Class II beta RFLP patterns with B haplotype, but not IrGAT, in the same line, suggesting that IrGAT is not controlled by MHC Class I or Class II beta genes.

Animals↗

PubMed2024

Local Ancestry at the Major Histocompatibility Complex Region is Not a Major Contributor to Disease Heterogeneity in a Multiethnic Lupus Cohort.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease resulting in debilitating clinical manifestations that vary in severity by race and ethnicity with a disproportionate burden in African American, Mestizo, and Asian populations compared with populations of European descent. Differences in global and local genetic ancestry may shed light on the underlying mechanisms contributing to these disparities, including increased prevalence of lupus nephritis, younger age of symptom onset, and presence of autoantibodies. METHODS: A total of 1,139 European, African American, and Mestizos patients with SLE were genotyped using the Affymetrix LAT1 World array. Global ancestry proportions were estimated using ADMIXTURE, and local ancestry was estimated using RFMIXv2.0. We investigated associations between lupus nephritis, age at onset, and autoantibody status with both global and local ancestry proportions within the Major Histocompatibility Complex region. RESULTS: Our results showed small effect sizes that did not meet the threshold for statistical significance for global or local ancestry proportions in either African American or Mestizo patients with SLE who presented with the clinical manifestations of interest compared with those who did not. CONCLUSION: These findings suggest that local genetic ancestry within the Major Histocompatibility Complex region is not a major contributor to these SLE manifestations among patients with SLE from admixed populations.

Humans↗

PubMed1991

Role of diversifying selection and gene conversion in evolution of major histocompatibility complex loci.

Genes at the major histocompatibility complex (MHC) in mammals are known to have exceptionally high polymorphism and linkage disequilibrium. In addition, these genes form highly complicated gene families that have evolved through gene conversion and unequal crossing-over. It has been shown recently that amino acid substitution at the antigen recognition site (ARS) is more rapid than synonymous substitution, suggesting some kind of positive natural selection working at the ARS. It is highly desirable to know the interactive effect of gene conversion and natural selection on the evolution and variation of MHC gene families. A population genetic model is constructed that incorporates both selection and gene conversion. Diversifying selection is assumed in which sequence diversity is enhanced not only between alleles at the same locus but also between duplicated genes. Expressed and nonexpressed loci are assumed as in the class I gene family of MHC, with gene conversion occurring among all loci. Extensive simulation studies reveal that very weak selection at individual amino acid sites in combination with gene conversion can explain the unusual pattern of evolution and polymorphisms. Here both gene conversion and natural selection contribute to enhancing polymorphism.

Alleles↗

PubMed2025

Major histocompatibility complex class IIB disassortative mate choice in a genetically monogamous seabird.

Among species reproducing sexually, mating strategies represent a major component of individual fitness. The major histocompatibility complex (MHC) is an extremely diverse set of genes responsible for immunological recognition and defence against pathogens. Although dissimilarity between mates at the major histocompatibility complex has been proposed to drive mate choice through increased offspring pathogen resistance, evidence is mixed. In addition, explorations of the role of the major histocompatibility complex in other mating strategies, such as divorce, are rare. We investigated whether dissimilarity at the major histocompatibility complex class IIB is associated with mate choice and divorce probability in the genetically monogamous black-legged kittiwake (Rissa tridactyla). We found that first-time male breeders, as well as divorced males, were paired with females more dissimilar at the major histocompatibility complex class IIB than expected under random mating. We did not find evidence for mate choice based on major histocompatibility complex class IIB dissimilarity when considering females. In addition, in the studied population, divorce probability was very low compared with other populations and did not significantly vary with the dissimilarity of the pair at the major histocompatibility complex class IIB. Our results pave the way to a better understanding of the complex role of major histocompatibility complex dissimilarity in mating decisions of species displaying mutual choice and biparental care.

Animals↗

PubMed1991

A cluster of transcribed sequences between the Pb and Ob genes of the murine major histocompatibility complex.

The region of the murine major histocompatibility complex (MHC) between the Pb (A beta 3) and Ob (A beta 2) genes controls the expression of an intracellular complex named the LMP (low molecular weight polypeptide) complex. DNA probes for at least seven different genes mapping to this region were isolated. These hybridize to a minimum of eight different transcripts ranging from approximately 1.3 to 3.7 kilobases (kb). The deduced amino acid sequences of the corresponding cDNAs indicate that three of these genes are new members of the MHC class II gene family. These genes are transcribed in a tissue-specific pattern similar to that of the traditional class II genes. Two of the remaining four genes, HAM1 and HAM2, are homologous to one another and to a family of eukaryotic and prokaryotic transport proteins and may be involved in antigen processing. The tissue distribution of HAM1 transcripts is consistent with its proposed role in class I-restricted antigen processing, whereas HAM2 transcription appears more restricted and may be involved in antigen processing for class II-restricted T cells. The HAM2 gene may produce two differentially spliced transcripts. The identity of the remaining two genes is not known. Analyses of transcript sizes, tissue distribution, sequence, and genetic mapping data suggest that none of these genes code for LMP antigens.

Animals↗

PubMed1991

Exogenous peptides compete for the presentation of endogenous antigens to major histocompatibility complex class II-restricted T cells.

Antigen-presenting cells (APC) transfected with a construct encoding the hen egg-white lysozyme (HEL) amino acid sequence 1-80 constitutively present HEL peptides complexed to major histocompatibility complex (MHC) class II molecules to specific T cell hybridomas, indicating that endogenous cellular antigens can be efficiently presented to class II-restricted T cells. Here we show that exogenous peptide competitors added to HEL-transfected APC can inhibit the presentation of endogenous HEL peptides to class II-restricted T cells. The inhibition is specific for the class II molecule binding the competitor peptide, and it affects to the same extent presentation of exogenous or endogenous HEL peptides. These results, demonstrating that an exogenous competitor can inhibit class II-restricted T cell activation induced by endogenous as well as exogenous antigen, suggest lack of strict compartmentalization between endogenous and exogenous pathways of antigen presentation. Since autoreactive T cells may recognize endogenous, as well as exogenous antigens, the results have implications for the treatment of autoimmune diseases by MHC blockade.

Actins↗