Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Major Histocompatibility Complex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,189 records · Page 66Linked to original sources
PubMed1987

Class II genes of the human major histocompatibility complex. Organization and evolutionary relationship of the DR beta genes.

The genes of the polymorphic HLA-DR molecules are located within the human major histocompatibility complex. We have studied the HLA-DR genes of an HLA homozygous individual typed to be DR4, Dw4, and DRw53. Fourteen cosmid and phage clones from genomic libraries were isolated and grouped into three clusters comprising a total of 165 kilobases. These clusters contain four DR beta genes. Nucleotide sequence determination showed that two of the genes encode beta chains that carry the DR4 and DRw53 specificities, respectively, while the other two genes are presumably pseudogenes. Comparisons of the nucleotide sequences of all four DR beta genes of the DR4 haplotype show that the genes are extensively similar, approximately 90% in both exons and introns. All four genes are equally similar to each other. These observations are consistent with the notion that the genes arose by duplications that were followed by homogenization through gene conversion. The existence of more than one DR beta gene homologue but only a single DR alpha gene homologue in mouse, rabbit, and cattle suggests that the DR beta gene duplications occurred at or early during mammalian speciation.

Base Sequence↗
PubMed1997

Assembly of an abundant endogenous major histocompatibility complex class II/peptide complex in class II compartments.

To identify the intracellular site(s) of formation of an endogenous class II/peptide complex in a human B cell line, we employed kinetic pulse-chase labeling experiments followed by subcellular fractionation by Percoll density gradient centrifugation and immunogold labeling on ultrathin cryosections. For direct demonstration of assembly of such complexes, we used the monoclonal antibody YAe, which detects an endogenous complex of the mouse class II molecule I-Ab with a 17-amino acid peptide derived from the alpha chain of HLA-DR (DR alpha52-68). We show that in human B lymphocytes, these class II/peptide complexes assemble and transiently accumulate in major histocompatibility complex class II-enriched compartments before reaching the cell surface.

Animals↗
PubMed1985

Evidence that polymorphism in the murine major histocompatibility complex may be generated by the assortment of subgene sequences.

The high degree of polymorphism found among the class I genes of the murine major histocompatibility complex (H-2) has led to the postulation that specific genetic mechanisms are responsible for their diversity. These same genetic mechanisms are probably responsible for the high spontaneous mutation frequency seen in H-2 alleles. The bml mutation of the H-2Kb gene has been shown to be 7 base pair changes over a 13 base pair region that result in three amino acid substitutions in the C1 domain of the protein product. The clustering of base-pair changes has suggested that the bm1 mutation resulted from a recombinational event analogous to gene conversion between the H-2Kb gene and a "donor" gene sequence. A 23-base oligonucleotide complementary to the bm1 mutant sequences was synthesized and used to probe genomic DNA restriction digests of the parental H-2b haplotype as well as other H-2 haplotypes. Our results indicate that a potential donor gene sequence is present in the genomes of all of the five mouse strains studied. Of eight tissues that were tested by blot-hybridization analysis, the potential donor gene sequences are transcribed only in the liver. Models for the generation of polymorphism among the H-2 class I genes via subgene rearrangements are proposed.

Animals↗
PubMed2001

Population genetics of the hispid cotton rat (Sigmodon hispidus): patterns of genetic diversity at the major histocompatibility complex.

The hispid cotton rat, Sigmodon hispidus, is a common rodent widely distributed across the southern USA and south into South America. To characterize major histocompatibility complex (MHC) diversity in this species and to elucidate large-scale patterns of genetic partitioning, we examined MHC genetic variability within and among 13 localities, including a disjunct population in Arizona and a population from Costa Rica that may represent an undescribed species. We also tested the hypothesis that populations within the USA are at equilibrium with regard to gene flow and genetic drift, resulting in isolation-by-distance. Using single-strand conformation polymorphism (SSCP) analysis we identified 25 alleles from 246 individuals. Gene diversity within populations ranged from 0.000 to 0.908. Analysis of molecular variance (AMOVA) revealed that 83.7% of observed variation was accounted for by within-population diversity and 16.3% was accounted for by among-population divergence. The disjunct population in Arizona was fixed for a single allele. The Costa Rican population was quite divergent based on allelic composition and was the only population with unique alleles. Within the main portion of the geographical distribution of S. hispidus in the USA there was considerable divergence among some populations; however, there was no significant pattern of isolation-by-distance overall (P = 0.090). Based on the significant divergence of the only sampled population to its east, the Mississippi River appears to represent a substantial barrier to gene flow.

Alleles↗
PubMed1984

Antibody-facilitated chimeras. Stem cell allotransplantation using antihost major histocompatibility complex monoclonal antibodies instead of lethal irradiation for host conditioning.

Complete hemopoietic takeover between semiallogeneic adults can be accomplished by the administration of antihost major histocompatibility complex (MHC) monoclonal antibody (mAb) and donor stem cells. The recipients of such treatment are termed antibody-facilitated chimeras, and they have been produced in (BALB/cCr----(BALB/cCr X C3H/HeJ)F1 and DBA/2J----(DBA/2J X C3H/HeJ)F1 strain combinations. Donor stem cells can be derived from spleen, bone marrow, or T-cell-depleted bone marrow. Engraftment by donor hemopoietic cells can be facilitated by mAbs directed toward class I (anti-H-2Kk) or class II (anti-H-2I-Ak) MHC antigens of the host. By monitoring isozymes of glucose phosphate isomerase, it can be shown that the establishment of donor hemopoiesis is stable, persisting for more than a year without graft-versus-host disease. The effect of anti-MHC mAb on pluripotential stem cells was evaluated by the (colony-forming units-spleen) (CFU-S) assay. The number of CFU-S in target (H-2k) bone marrow was reduced by in vitro pretreatment with anti-H-2Kk mAb, but not with anti-H-2I-Ak mAb. In contrast, in vivo administration of either anti-H-2Kk or anti-H-2I-Ak mAb resulted in a marked decrease in the CFU-S capacity of relevant strain mice. These observations suggest that the target of the in vivo mAb treatment may be pluripotential stem cells--or perhaps the hemopoietic microenvironment.

Animals↗
PubMed1987

Molecular analysis of the chicken major histocompatibility complex gene and gene products.

New technologies are enabling researchers to conduct analysis of the molecular structure of the genes and gene products of the major histocompatibility complex (MHC). Two of these new technologies are the production of monoclonal antibodies by hybridomas and analysis of deoxyribonucleic acid (DNA) by restriction fragment length polymorphisms (RFLP) on Southern blots. Monoclonal antibodies, because of their exquisite specificity, can be used to isolate purified MHC antigens for further study. The RFLP analysis can be used to examine differences in the MHC at the DNA level. This paper describes the two aforementioned technologies and their application to molecular analysis of the chicken MHC.

Animals↗
PubMed1999

Interaction of Brucella abortus lipopolysaccharide with major histocompatibility complex class II molecules in B lymphocytes.

Lipopolysaccharide (LPS), a major amphiphilic molecule located at the outer membrane of gram-negative bacteria, is a potent antigen known to induce specific humoral immune responses in infected mammals. LPS has been described as a polyclonal activator of B lymphocytes, triggering the secretion of antibodies directed against distinct sugar epitopes of the LPS chain. But, how LPS is handled by B cells remains to be fully understood. This task appears to be essential for a better knowledge of the anti-LPS humoral immune response. In this study, we examine the internalization of LPS and its interaction with antigen-presenting major histocompatibility complex (MHC) class II molecules in murine and human B-cell lines. By use of immunofluorescence, we observe that structurally different LPSs from Brucella and Shigella strains accumulate in an intracellular compartment enriched in MHC class II molecules. By use of immunoprecipitation, we illustrate that only Brucella abortus LPS associates with MHC class II molecules in a haplotype-independent manner. Taken together, these results raise the possibility that B. abortus LPS may play a role in T-cell activation.

Animals↗
PubMed1995

Analysis of the fine specificities of sheep major histocompatibility complex class II-specific monoclonal antibodies using mouse L-cell transfectants.

The fine specificities of two panels of monoclonal antibodies (mAbs) for sheep major histocompatibility complex (MHC) class II molecules were determined using five mouse L-cell transfectants, each expressing a defined sheep DQ or DR MHC class II A/B gene pair. Using the transfectants in an indirect fluorescence antibody assay, previous immunochemical characterization of the mAbs was confirmed for 16 of 23 mAbs tested. The MHC class II subtype specificity (DQ or DR) of each mAb was assigned without interference from the products of other expressed class II loci. This allowed the identification of both cross-locus specificities as well as defining fine specificities of mAbs previously only partially characterized by immunochemical techniques.

Amino Acid Sequence↗
PubMed1986

Major histocompatibility complex influences reproductive efficiency: evolutionary implications.

Measurements of six reproductive characteristics revealed differences in seven congenic mouse strains with genetic differences in H-2, the major histocompatibility complex (MHC). Associations between reproductive efficiency and MHC has evolutionary implications. One association explains the uneven distribution and heterozygosity of MHC alleles in wild mouse and human populations. The second is based on links between MHC and hormonal sensitivities that regulate an individual's responses to the environment. MHC may be a seat of genotypic-environmental interactions that guide natural selection.

Alleles↗
PubMed2004

Peptide binding at class I major histocompatibility complex scored with linear functions and support vector machines.

We explore two different methods to predict the binding ability of nonapeptides at the class I major histocompatibility complex using a general linear scoring function that defines a separating hyperplane in the feature space of sequences. In absence of suitable data on non-binding nonapeptides we generated sequences randomly from a selected set of proteins from the protein data bank. The parameters of the scoring function were determined by a generalized least square optimization (LSM) and alternatively by the support vector machine (SVM). With the generalized LSM impaired data for learning with a small set of binding peptides and a large set of non-binding peptides can be treated in a balanced way rendering LSM more successful than SVM, while for symmetric data sets SVM has a slight advantage compared to LSM.

Amino Acid Sequence↗
PubMed1992

Inhibition of expression of major histocompatibility complex class II molecules in macrophages infected with Leishmania donovani occurs at the level of gene transcription via a cyclic AMP-independent mechanism.

Among the important pleiotropic responses to gamma interferon (IFN-gamma) during the activation of macrophages (M phi) is the increased expression of major histocompatibility complex class II genes. In the present study, infection with Leishmania donovani was shown to inhibit in parallel the induction by IFN-gamma of H-2 A beta gene transcription, class II mRNA accumulation, and H-2 Ad protein expression in cells of the murine macrophage cell line P388D1. Treatment of P388D1 cells with either the adenylate cyclase activator cholera toxin or the protein kinase A activator N6-2'-O-dibutyryl cyclic AMP (dibutyryl cAMP) similarly inhibited the induction by IFN-gamma of class II protein expression, and in parallel with Leishmania infection, cholera toxin inhibited the induction of mRNA for the H-2 A alpha and H-2 A beta proteins. Concentrations of intracellular cAMP were significantly increased in cholera toxin-treated cells but not in leishmania-infected cells. These findings indicate that at least one mechanism by which Leishmania infection attenuates the activation of M phi by IFN-gamma involves selective, transcriptional inhibition of major histocompatibility complex class II genes via a cAMP-independent mechanism.

Animals↗
PubMed1995

Rat mitochondrial aldehyde dehydrogenase polymorphism and major histocompatibility complex RT1.A phenotypes are not associated with alcohol drinking in P and NP rats.

Previous studies revealed polymorphisms in mitochondrial aldehyde dehydrogenase (ALDH2) and the major histocompatibility complex RT1.A that appeared in association with alcohol drinking preference in the alcohol-preferring (P) and alcohol-nonpreferring (NP) rat lines. To determine the strength of these associations, the P and NP lines were crossed, and cosegregation studies were performed in the F2 progeny. The ALDH2Q allele and the ALDH2R allele, found in the P and NP lines, respectively, were found not to be associated with the high and low drinking animals in the F2 progeny. Kinetic studies with ALDH2Q and ALDH2R isozymes purified from the mitochondria of P and NP rat livers, respectively, showed that the polymorphism would not be expected to be associated with altered aldehyde metabolism. The association between RT1.A and alcohol preference (RT1.Auu with high and RT1.AII with low alcohol intake) also could not be confirmed in the segregating F2 progeny of the P x NP intercross.

Alcohol Drinking↗
PubMed1994

Altered major histocompatibility complex restriction in the NK1.1+Ly-6Chi autoreactive CD4+ T cell subset from class II-deficient mice.

We previously demonstrated selective enrichment of major histocompatibility complex (MHC) class II-specific autoreactive T cells in a subset of mouse CD4+ thymocytes. Here we show that a significant fraction of these autoreactive cells in the normal adult thymus expresses NK1.1 and high levels of Ly-6C and also exhibits flexibility in MHC restriction. In normal mice, this NK1.1+Ly-6Chi subfraction accounts for 10-50% of the CD4+ autoreactive subset and is enriched for MHC class II-restricted autoreactive cells as determined by mixed leukocyte reaction frequency analysis, similar to NK1.1-Ly-6C-CD4+ autoreactive cells. In contrast, in the thymus of class II-deficient littermate mice, NK1.1+Ly-6Chi cells account for most of the mature heat stable antigen (HSA)-CD4+ fraction and exhibit MHC-restricted non-class II autoreactivity. Thus, NK1.1+Ly-6ChiCD4+ T cells show flexibility in MHC class restriction, but their autoreactivity remains MHC dependent.

Aging↗
PubMed1985

The major histocompatibility complex of the cynomolgus monkey. II. Polymorphism at three serologically defined loci and correlation of haplotypes with stimulation in MLC and skin graft survival.

The major histocompatibility complex (MHC) of the cynomolgus monkey has been further characterized by testing in population and family studies 50 new alloantisera along with previously characterized sera. This resulted in the redefinition of three of the original 21 CyLA specificities and the identification of 14 additional specificities. Genetic evidence for the existence of a third class I locus, designated CyLa-C, is presented together with evidence for the linkage of a locus-controlling allostimulation of mixed lymphocyte cultures (MLC) to this complex. The number of alleles assigned to the CyLA-A locus was increased from seven to 14, the B locus from six to ten, and the newly defined C locus was assigned six alleles. Haplotype and gene frequencies were counted from the family data and compared with estimates from the population. Several examples of linkage disequilibrium were noted, though this does not appear to be a pronounced feature of the system. One informative family was identified in which a recombination resulted in the segregation of the MLC response with CyLA-A thus, implying that this may be the homologue of the B locus of other primate systems. In addition to the linkage of an MLC locus to CyLA, further evidence that this is the cynomolgus MHC came from the effect of haplotype matching on the survival of skin grafts exchanged within families. An increase in the mean graft survival time was dependent upon the number of haplotypes matched. The organization and degree of polymorphism of the cynomolgus MHC was shown to be homologous to other primate systems, which should allow this species to serve as a substitute for the rhesus macaque as a genetically defined model in transplantation and immunology research.

Alleles↗
PubMed1992

Major histocompatibility complex class I-specific and -restricted killing of beta 2-microglobulin-deficient cells by CD8+ cytotoxic T lymphocytes.

Cytotoxic T lymphocytes (CTLs) recognize major histocompatibility complex (MHC) class I molecules, normally composed of a heavy chain, a beta 2-microglobulin (beta 2m), and peptide antigens. beta 2m is considered essential for the assembly and intracellular transport of MHC class I molecules as well as their peptide presentation to CTLs. Contrary to this dogma, we now report the generation of allospecific and restricted CD8+ and TCR alpha beta+ CTLs (where TCR is T-cell receptor) capable of killing beta 2m-deficient cells. Such CTLs were obtained by priming mice with live allogeneic beta 2m- spleen cells or mutant lymphoma cells producing MHC class I protein but no detectable beta 2m. Although both beta 2m- and beta 2m-expressing lymphoma cells were rejected in allogeneic mice, only the former were efficient inducers of CTLs recognizing beta 2m- cells. These CTLs were MHC class I (H-2Kb or Db)-specific and CD8-dependent and did not require serum as a source of external beta 2m in the culture. They could be induced across major and minor histocompatibility barriers. The H-2-restricted CTLs generated in the latter case failed to kill the antigen-processing-deficient target RMA-S cells. The results show that MHC class I heavy chains in beta 2m- cells can be transported to the cell surface and act as antigens or antigen-presenting molecules to allospecific and MHC-restricted CTLs.

Animals↗
PubMed1992

A common antiviral cytotoxic T-lymphocyte epitope for diverse major histocompatibility complex haplotypes: implications for vaccination.

Of nine established murine haplotypes, mice of three types (H-2d, H-2u, and H-2q) possess major histocompatibility complex class I glycoproteins able to present an identical viral peptide for recognition and lysis by virus-specific cytotoxic T lymphocytes. Incorporation of this viral epitope into a recombinant vaccinia vaccine and administration of a single dose protects mice with these three haplotypes from an ordinarily lethal challenge of virus. Hence, a common epitope can exist. The sharing of the ability to bind such epitopes among different MHC haplotypes underscores the feasibility of developing an effective cytotoxic T-lymphocyte vaccine for outbred populations like humans.

Amino Acid Sequence↗
PubMed1990

Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules.

The human CD4 molecule binds both human immunodeficiency virus envelope protein gp120 and class II major histocompatibility complex (MHC) molecules. We have studied a series of mutants in the region of amino acids 42-49 of CD4 for their ability to bind gp120, to interact with class II MHC, to enhance T-cell activation, and to bind a panel of anti-CD4 antibodies. The mutation Q40P (Gln40----Pro) and the deletion d42-49 were found to disrupt most antibody epitopes in the V1 domain of CD4, suggesting major conformational changes, whereas mutants F43L, G47R, and P48S retained the binding of most of the anti-CD4 antibodies tested. The mutants d42-49, Q40P, F43L, and G47R lost both gp120 and class II MHC binding as well as the ability to enhance T-cell activation. In contrast, the mutation P48S affected neither gp120 binding, nor class II MHC binding, nor T-cell activation. We conclude that within this region the binding sites for gp120 and for class II MHC molecules overlap and that amino acids Phe43 and Gly47 comprise an intimate part of both binding sites. These observations are consistent with a three-dimensional model of the V1 domain of CD4 that was developed in order to understand the structural basis for binding to CD4.

Amino Acid Sequence↗
PubMed1991

Expression and induction of intercellular adhesion molecules (ICAMs) and major histocompatibility complex (MHC) antigens on cultured murine oligodendrocytes and astrocytes.

Expression of intercellular adhesion molecule-1 (ICAM-1), ICAM-2-like molecule (Lgp55), and class I/II major histocompatibility complex (MHC) antigens (H-2 and Ia) was investigated in cultures of murine oligodendrocytes and astrocytes. Under unstimulated conditions, low levels of ICAM-1 expression were observed on astrocytes (less than 20%), but not on oligodendrocytes. Lgp55 was expressed intensely on oligodendrocytes (greater than 90%) and to a lesser degree on astrocytes (greater than 70%). A weak class I MHC (H-2) immunoreactivity was identified on both oligodendrocytes and astrocytes (50-70%). Class II MHC (Ia) antigen was undetectable on both cell types. After 48-hr exposure to immune mediators that include interferon-gamma (IFN-gamma), 500 U/ml, and supernatant from concanavalin A (Con A)-activated spleen cells, ICAM-1 expression was markedly increased on astrocytes (greater than 80%), but not on oligodendrocytes. Lgp55 expression on both cell types was not altered. Induction of H-2 antigen expression by immune mediators was quite high on both cell types (greater than 95%), while Ia antigen induction was low on astrocytes (less than 50%) and did not occur on oligodendrocytes. Cell type-specific expression and induction of ICAMs and MHC antigens by immune mediators may play roles in lymphocyte-glial cell interactions at the sites of inflammation in the central nervous system (CNS).

Animals↗