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 901 records · Page 50Linked to original sources
PubMed1989

The alpha 3 domain of major histocompatibility complex class I molecules plays a critical role in cytotoxic T lymphocyte stimulation.

Allogeneic major histocompatibility complex class I molecules induce strong cytotoxic T lymphocyte (CTL) responses whereas xenogeneic molecules do not. We have tested a series of mouse/human hybrid molecules for their ability to stimulate mouse CTL. The molecules with murine alpha 3 domains consistently stimulated stronger CTL responses than those with human alpha 3 domains, independent of the species origin of the N-terminal alpha 1 or alpha 2 domains. We have found that the ability of class I molecules to induce strong cytotoxic responses correlates positively with their ability to stimulate expansion of the CD8+CD4-T cell subset. The results indicate that mouse T cells can recognize class I molecules with human alpha 1 and/or alpha 2 domains, but for efficient stimulation of these T cells it is important that the immunizing molecule contains a murine alpha 3 domain. We suggest that T cell priming requires an efficient interaction of CD8 with the class I alpha 3 domain, and this shows some species restriction.

Animals↗
PubMed1991

Polarized expression of major histocompatibility complex class I molecules in human endometrial and endocervical epithelial cells.

The localization of major histocompatibility complex (MHC) class I molecules in human endometrial and endocervical epithelial cells was studied with an immunogold technique on ultrathin cryosections. At the cell surface, MHC class I molecules are delivered solely to the basolateral plasma membrane in human epithelia. Therefore, only the basolateral domain of epithelial cells is capable of presenting antigen to MHC class I-restricted cytotoxic T cells.

Adult↗
PubMed1997

Characterizing immunodominant and protective influenza hemagglutinin epitopes by functional activity and relative binding to major histocompatibility complex class II sites.

In the present study the analysis of functional activity and major histocompatibility complex (MHC) binding of two adjacent MHC class II-restricted epitopes, located in the C-terminal 306-329 region of human influenza A virus hemagglutinin 1 subunit (HA1) conserved with subtype sequences and not affected by antigenic drift, was undertaken to explore the hierarchy of local immunodominance. The functional activity of two T cell hybridomas of the memory/effector Th1 phenotype in combination with in vivo immunization studies provided a good tool for investigating the functional characteristics of the T cell response. The in vitro binding assays performed with a series of overlapping, N-terminal biotinylated peptides covering the 306-341 sequence enabled us to compare the relative binding efficiency of peptides, comprising two distinct epitopes of this region, to I-Ed expressed on living antigen-presenting cells. Our studies revealed that (i) immunization of BALB/c mice with the 306-329 H1 or H2 peptides resulted in the activation and proliferation of T cells recognizing both the 306-318 and the 317-329 epitopes, while the 306-329 H3 peptide elicits predominantly 306-318-specific T cells, (ii) the 317-329 HA1 epitope of the H1 and H2 but not the H3 sequence is recognized by T cells and is available for recognition not only in the 317-329 peptide but also in the extended 306-329 or 306-341 peptides, (iii) the 306-318 and the 317-329 hemagglutinin peptides encompassing the H1, H2 but not the H3 sequence bind with an apparently similar affinity to and therefore compete for I-Ed binding sites, and (iv) the 317-341, the 317-329 peptides and their truncated analogs show subtype-dependent differences in MHC binding and those with lower binding capacity represent the H3 subtype sequences. These results demonstrate that differences in the binding capacity of peptides comprising two non-overlapping epitopes located in the C-terminal 306-329 region of HA1 of all three subtype-specific sequences to MHC class II provide a rationale for the local and also for the previously observed in vivo immunodominance of the 306-318 region over the 317-329 epitope in the H3 but not in the H1 or H2 sequences. In good correlation with the results of the binding and functional inhibition assays, these data demonstrate that in the H1 and H2 subtypes both regions are available for T cell recognition, they compete for the same restriction element with an apparently similar binding efficiency and, therefore, function as co-dominant epitopes. Due to the stabilizing effect of the fusion peptide, peptides comprising the 306-341 or 317-341 H1 sequences are highly immunogenic and elicit a protective immune response which involves the production of antibodies and interleukin-2 and tumor necrosis factor producing effector Th1 cells both directed against the 317-329 region. Based on the similarity of the I-Ed and HLA-DR1 peptide binding grooves and motifs, these results suggest that amino acid substitutions inserted to the H3 subtype sequence during viral evolution can modify the relative MHC binding capacity and invert the local hierarchy of immunodominance of two closely situated epitopes that are able to bind to the same MHC class II molecule.

Amino Acid Sequence↗
PubMed1990

Major histocompatibility complex class I genes of Peromyscus leucopus.

Class I genes of the Peromyscus leucopus major histocompatibility complex (MhcPele) were examined by Southern blot hybridization, genomic cloning, and DNA sequencing. At least three distinct subtypes of Pele class I genes were discerned, which we have designated Pele-A, B, and C. The nucleotide sequences of exon 5-containing regions (encoding the transmembrane domain) suggested that Pele-A genes are homologs of mouse H-2K, D, L, and Q genes and that Pele-B genes correspond to mouse Tla genes. The Pele-C genes appeared similar to mouse M1 genes. The number of unique genes in each subtype cloned from an individual P. leucopus were 20 for Pele-A, 13 for Pele-B, and 2 for Pele-C. Three genomic clones showed cross-hybridization to both Pele-A and Pele-B gene-specific probes. Six genomic clones remained unclassified as they did not cross-hybridize to exon 5-containing probes from Pele-A, B, or C genes. The homology between the transmembrane domains of Pele class I gene subtypes was found to be similar to that observed between the transmembrane domains of H-2 subtypes (or groups). Interspecific similarity of exon 5 was found to be 81%-88% between Pele class I genes and their H-2 counterparts.

Animals↗
PubMed1988

Interferon-induced expression of class II major histocompatibility antigens in the major histocompatibility complex (MHC) class II deficiency syndrome.

Class II antigens encoded by genes of the major histocompatibility complex (MHC) are expressed by a variety of cell types and have a vital role in the cellular interactions required for an effective immune response. We have analyzed the regulation of HLA-DR, DP, and DQ class II antigen expression on cells of different lineage from an immunodeficient patient with the MHC class II deficiency syndrome. T and B lymphocytes, monocytes, and fibroblasts, which initially expressed no class II antigens, were treated with inductive stimuli that normally lead to enhanced expression of class II antigens. Monocytes, but not fibroblasts, cultured for 48-96 hr in the presence of recombinant gamma interferon expressed all three types of class II antigens. In contrast, T lymphocytes did not express class II antigens following their exposure to a variety of stimuli, including activation with phytohemagglutinin and culture in the presence of interleukin-2, transformation by the retrovirus HTLV-1 or HTLV-2, or exposure to the demethylating agent 5-azacytidine. Similarly, class II antigens were not induced on B cells by cross-linkage of surface immunoglobulin molecules with anti-mu, exposure to Epstein-Barr virus, or treatment with soluble factors secreted by activated T cells. These results demonstrate that the regulation of class II MHC antigen expression by monocytes and lymphocytes is dissimilar and suggest that different regulatory genes are involved in the control of class II antigen expression by cells of different lineage.

Adult↗
PubMed1993

Genes of the major histocompatibility complex and the evolutionary genetics of lifespan.

Mice that presumably differ just in the major histocompatibility complex (MHC) chromosomal region provide the best evidence that MHC genes affect lifespan. Further evidence is that MHC region genes in some cases are known to influence reproduction, growth, and development. Moreover, MHC genetic associations with disease are well documented. This paper summarizes and defines aspects of the molecular biology, cellular function, and evolution of MHC genes (with special emphasis on the polymorphic MHC class I and II genes) which are important in aging, and attempts to integrate these into an evolutionary genetic perspective of senescence. It is suggested that MHC genes provide a mammalian paradigm for the genetics of lifespan because of their intra- and interspecies diversification, evolutionary selection, and age-specific effects.

Amino Acid Sequence↗
PubMed2006

Major histocompatibility complex variation in the endangered crested ibis Nipponia nippon and implications for reintroduction.

The major histocompatibility complex (MHC), with its extraordinary levels of genetic variation, is thought to be an essential aspect of the ability of an organism to recognize different parasites and pathogens. It has also been proposed to regulate reproductive processes in many aspects. Here we examine the genetic variation of the second exon of the MHC class II B genes of the crested ibis, an endangered species known to descend from just two breeding pairs rediscovered in 1981. Only five alleles are identified by single-strand conformation polymorphism (SSCP) analysis of 36 samples taken from both wild and captive populations, and a comparatively low level of divergence between MHC alleles is observed. We suggest that representative sampling of individuals with most of the different MHC allele genotypes to constitute a founder population, together with the monitoring of the pathogen status of candidate sites before release, is of great importance for raising the success rate of reintroduction for the crested ibis.

Amino Acid Sequence↗
PubMedDate not supplied

Differential expression of class II major histocompatibility complex and Thy 1.2 antigens on mouse decidua.

A differential expression of class II major histocompatibility complex (MHC) and Thy 1.2 antigens was detected on two morphologically distinct cell populations in short-term cultures of murine decidual tissue. Stromal type decidual cells expressed Thy 1.2, albeit transiently, and consistently lacked class II antigens. By contrast decidual macrophages expressed class II antigens and lacked Thy 1.2 antigens. Stromal type decidual cells, after culture in the presence of indomethacin, displayed no evidence of prostaglandin-mediated modulation of class II expression. These findings suggest that class II positive decidual macrophages are responsible for the antigen-presenting capacity of decidua.

Animals↗
PubMed1989

Influenza virus changes cell-surface glycoproteins including major histocompatibility complex determinants on lymphocytes.

The effect of influenza virus infection on the expression of major histocompatibility complex (MHC) antigens was investigated. Infection with influenza virus resulted in an increase of the binding of anti-MHC class I and class II antibodies to resting T cells. The binding of anti-MHC class II antibodies to activated T cells was increased approximately threefold. The binding of anti-MHC class I and class II antibodies to Epstein-Barr virus-transformed B cells appeared unaffected after influenza virus infection. Recombinant human interferon-alpha and/or -gamma added to T cells did not enhance the binding of anti-MHC antibodies. Biochemical analysis revealed no increase in the amount of class I and class II antigens as a consequence of viral infection, but a marked decrease in sialic acid content was found, most probably caused by the viral neuraminidase. Pulse-chase experiments suggest that the viral neuraminidase can catalyze the removal of sialic acids both en route to and at the cell surface. The absence of sialic acid residues can explain the increased binding of anti-MHC antibodies, because neuraminidase (clostridium perfringens) treatment of T and Epstein-Barr virus-transformed B cells resulted in a shift in both isoelectric point and antibody binding similar to that observed after influenza virus infection.

Antibodies, Monoclonal↗
PubMed1998

Expression of major histocompatibility complex class II antigens in the canine intestine.

Immunohistochemical techniques were used to assess major histocompatibility complex (MHC) class II expression by enterocytes and lamina propria cells in the canine intestinal tract. Duodenal enterocyte class II expression was faint and limited to the lower crypt region whereas jejunal and ileal enterocyte expression was stronger, being present in both crypt and villus areas. Enterocyte staining was of greatest intensity in crypts adjacent to Peyer's patches and intense membrane staining of most Peyer's patch lymphocytes was also seen. Enterocyte MHC class II expression in the colon was largely limited to the lower crypt region. Within the lamina propria, of all intestinal sites examined, a heterogeneous population of cells were MHC class II positive and these had morphological features of macrophages and dendritic cells. Lymphocytes, plasma cells, fibroblasts and vascular endothelium were not stained. Definition of constitutive expression of MHC class II within the canine intestine may be important in identifying upregulation of this molecule in inflammatory bowel diseases.

Animals↗
PubMed2001

Induction of major histocompatibility complex class I molecules on human neuroblastoma line cells by a flavoid antioxidant.

Human major histocompatibility complex (MHC) class I expression is usually suppressed in neuronal cells and neuroblastoma cells. In the present study, we analyzed the effect of a flavonoid antioxidant, silymarin, on the induction of MHC class I molecules in human neuroblastoma line cells. Treatment of neuroblastoma cells with silymarin resulted in the expression of MHC class I molecules. Silymarin treatment enhanced the transcriptional activity of the reporter construct containing MHC class I promoter truncated within -428 bp of transcription initiation, but not the construct containing the promoter truncated within -284 bp. Because an E-box element is located between -428 and -285 bp of the transcription initiation, results suggest that silymarin acts on the enhancer activity of the E-box in the MHC class I promoter. Our findings indicate that silymarin induces the transcriptional factors to enhance the MHC class I promoter through the class I E-box element.

Antioxidants↗
PubMed2002

Modeling alternative binding registers of a minimal immunogenic peptide on two class II major histocompatibility complex (MHC II) molecules predicts polarized T-cell receptor (TCR) contact positions.

Several major histocompatibility complex class II (MHC II) complexes with known minimal immunogenic peptides have now been solved by X-ray crystallography. Specificity pockets within the MHC II binding groove provide distinct peptide contacts that influence peptide conformation and define the binding register within different allelic MHC II molecules. Altering peptide ligands with respect to the residues that contact the T-cell receptor (TCR) can drastically change the nature of the ensuing immune response. Here, we provide an example of how MHC II (I-A) molecules may indirectly effect TCR contacts with a peptide and drive functionally distinct immune responses. We modeled the same immunogenic 12-amino acid peptide into the binding grooves of two allelic MHC II molecules linked to distinct cytokine responses against the peptide. Surprisingly, the favored conformation of the peptide in each molecule was distinct with respect to the exposure of the N- or C-terminus of the peptide above the MHC II binding groove. T-cell clones derived from each allelic MHC II genotype were found to be allele-restricted with respect to the recognition of these N- vs. C-terminal residues on the bound peptide. Taken together, these data suggest that MHC II alleles may influence T-cell functions by restricting TCR access to specific residues of the I-A-bound peptide. Thus, these data are of significance to diseases that display genetic linkage to specific MHC II alleles, e.g. type 1 diabetes and rheumatoid arthritis.

Alleles↗
PubMedDate not supplied

Major histocompatibility complex class I molecules internalized via coated pits in T lymphocytes.

Endocytosis of the major histocompatibility complex (MHC)-encoded class I and class II molecules has been the subject of recent investigations. Class I molecules, which are key elements in T cell-mediated cytotoxicity, are differentially endocytosed by different cell types. Fibroblasts internalize their class I molecules via uncoated cell surface vesicles and tubular invaginations when these molecules are cross-linked with multivalent ligands. T lymphocytes internalize their class I molecules spontaneously, but B lymphocytes do not internalize them at all. Here we describe a morphological investigation of the mechanism by which class I molecules are endocytosed by T lymphocytes. We show that, unlike fibroblasts, T lymphocytes spontaneously internalize 20-40% of their class I molecules in a process involving coated pits and coated vesicles. Thus, the endocytic pathway of class I molecules in T lymphocytes is similar to those of other more classical cell-surface receptors involved in receptor-mediated endocytosis. In contrast, the same class I molecules remained on the cell surface in B lymphocytes. These data show that class I molecules are differentially regulated in T and B lymphocytes and fibroblasts.

Animals↗
PubMed1985

Distribution of the major histocompatibility complex antigens in human and rat kidney.

We have compared the distribution of the major histocompatibility complex (MHC) antigens in human and rat kidney using monospecific antisera to class I and II antigens of the MHC. FITC/TRITC double immunofluorescence was used to demonstrate these antigens in frozen sections and the Staphylococcus aureus Cowan I rosette assay on the cell surface. In both species, the MHC antigens were prominently present on the passenger leukocytes. Immunofluorescence analysis of human kidney demonstrated that the class I, beta 2-microglobulin (beta 2m), and class II antigens were present in the vascular endothelial cells and class I antigens in the renal tubular cells. The Staphylococcus assay demonstrated that these antigens were also exposed on the respective cell surfaces. In clear contrast, in the rat, class I, the beta 2m, and class II antigens were absent from the kidney vascular endothelium of large vessels and intertubular capillaries; however, large amounts of class II antigens were seen inside the proximal renal tubular cells. The Staphylococcus assay indicated that none or very little of these antigens were exposed on the kidney parenchymal cell surface. These differences may explain why rat renal transplants are relatively non-immunogenic and easily accepted, whereas human renal transplant recipients must be immunosuppressed ad infinitum.

Animals↗
PubMed2003

A differential requirement for phosphoinositide 3-kinase reveals two pathways for inducible upregulation of major histocompatibility complex class II molecules and CD86 expression by murine B lymphocytes.

Constitutive expression of major histocompatibility complex class II molecules (MHC II) is restricted to dendritic cells, cells of the macrophage lineage and B lymphocytes. In all three lineages, peptide fragments of captured antigen are loaded into newly synthesized MHC II molecules. In B-lineage cells, MHC II synthesis is dramatically increased on encounter with antigen, by T-cell-derived signals and by microbial products. We have previously shown that immature B cells fail to hyperexpress MHC II after antigen receptor [B-cell receptor (BCR)] ligation, but are responsive to other stimuli. Expression of the costimulatory molecule, CD86, was similarly regulated. This suggested the existence of two pathways regulating expression of these important molecules. Here we present data supporting this hypothesis. We show that activity of the enzyme phosphatidylinositol 3-kinase is critical for MHC II hyperexpression and induction of CD86 in response to ligation of the BCR or CD38, but not for responses to other stimuli including interleukin-4, lipopolysaccharide and CD40 ligation.

Animals↗
PubMed2001

Comparative analysis of population structure across environments and geographical scales at major histocompatibility complex and microsatellite loci in Atlantic salmon (Salmo salar).

Evidence of selection acting on major histocompatibility complex (MHC) genes has been illustrated with the analysis of their nucleotide sequences and allele frequency distribution. Comparing the patterns of population differentiation at neutral markers and MHC genes in the wild may provide further insights about the relative role of selection and neutrality in shaping their diversity. In this study, we combine both methods to assess the role of selection on a MHC gene in Atlantic salmon. We compare variation at a MHC class II B locus and microsatellites among 14 samples from seven different rivers and seven subpopulations within a single river system covering a variety of habitats and different geographical scales. We show that diversifying selection is acting on the sites involved in antigen presentation and that balancing selection maintains a high level of polymorphism within populations. Despite important differences in habitat type, the comparison of the population structure at MHC and microsatellites on large geographical scales reveals a correlation between patterns of differentiation, indicating that drift and migration have been more important than selection in shaping population differentiation at the MHC locus. In contrast, strong discrepancies between patterns of population differentiation at the two types of markers provides support for the role of selection in shaping population structure within rivers. Together, these results confirm that natural selection is influencing MHC gene diversity in wild Atlantic salmon although neutral forces may also be important in their evolution.

Alleles↗
PubMed1985

Molecular association between major histocompatibility complex class I antigens and insulin receptors in mouse liver membranes.

Molecular association between major histocompatibility complex (MHC) antigens and cellular proteins are thought to be involved in various immunological and nonimmunological functions of MHC antigens, including hormone signaling. The existence of physical interactions between insulin receptors and MHC class I antigens was investigated in liver plasma membranes from congenic H-2k mice. Insulin receptors were specifically labeled with a 125I-labeled photoreactive insulin analogue, and cellular proteins were solubilized and incubated with various monoclonal antibodies. Immunoprecipitates were analyzed by polyacrylamide gel electrophoresis followed by autoradiography. Antibodies reacting with distinct epitopes on H-2k class I antigens were all able to precipitate up to 25% of the labeled insulin receptors in H-2k mouse liver membranes, whereas no insulin receptors were precipitated in H-2b mouse liver membranes. Sequential immunoprecipitations showed that insulin receptors and H-2 antigens were coprecipitated and that no cross-reactivity occurred. The specificity of the interaction between insulin receptors and H-2 antigens was demonstrated after double labeling of membrane proteins by photoreactive insulin and lactoperoxidase-catalyzed iodination. These results thus show that, in mouse liver membranes, insulin receptors are physically associated to class I antigens of the MHC.

Animals↗
PubMed1992

Induction of immunity and oral tolerance with polymorphic class II major histocompatibility complex allopeptides in the rat.

We studied the immunogenicity and tolerogenicity of class II major histocompatibility complex (MHC) allopeptides in the rat. Inbred LEW (RT1l) rats, used as responders, were immunized in the foot pad with a mixture of eight synthetic class II MHC allopeptides emulsified in complete Freund's adjuvant. These sequences represent the full-length second domain of RT1.Bu and RT1.Du (WF) beta chains. In vitro, responder lymphocytes harvested from popliteal and inguinal lymph nodes of immunized animals exhibited significant proliferation to the MHC allopeptide mixture. In addition, these responder lymphocytes had significantly increased proliferation to allogeneic WF (RT1u) stimulator cells, when compared to naive controls in the standard one-way mixed lymphocyte response. In vivo, peptide-immunized LEW animals were challenged in the ear 2 weeks after immunization with the allopeptide mixture, the individual allopeptide sequences, or allogeneic WF splenocytes. When compared to controls, these animals had significant delayed-type hypersensitivity responses to the allopeptide mixture, to the beta-pleated sheet allopeptide sequences, and to allogeneic WF splenocytes but not to the alpha-helix allopeptide sequences, to syngeneic LEW splenocytes, or to third party allogeneic BN splenocytes. Oral administration of the allopeptide mixture to LEW responder rats daily for 5 days before immunization effected significant reduction of delayed-type hypersensitivity responses both to the allopeptide mixture and to allogeneic splenocytes. This reduction was antigen-specific, since there was no reduction of delayed-type hypersensitivity responses to mycobacterium tuberculosis. These data demonstrate that lymphocytes from animals immunized with polymorphic class II MHC allopeptides can recognize and proliferate to the same amino acid sequences on allogeneic cell surface MHC molecules. In addition, oral administration of these peptides down-regulates the systemic cell-mediated immune response in a specific fashion. Synthetic MHC allopeptides should allow the study of alloimmunity in vivo, including induction of immune tolerance.

Amino Acid Sequence↗