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Results for “major histocompatibility complex”

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At least 19 recordsLinked to original sources

PubMed1996

Antigen processing and presentation by the class I major histocompatibility complex.

Major histocompatibility complex (MHC) class I molecules bind peptides derived from cellular proteins and display them for surveillance by the immune system. These peptide-binding molecules are composed of a heavy chain, containing an antigen-binding groove, which is tightly associated with a light chain (beta 2-microglobulin). The majority of presented peptides are generated by degradation of proteins in the cytoplasm, in many cases by a large multicatalytic proteolytic particle, the proteasome. Two beta-subunits of the proteasome, LMP2 and LMP7, are inducible by interferon-gamma and alter the catalytic activities of this particle, enhancing the presentation of at least some antigens. After production of the peptide in the cytosol, it is transported across the endoplasmic reticulum (ER) membrane in an ATP-dependent manner by TAP (transporter associated with antigen presentation), a member of the ATP-binding cassette family of transport proteins. There are minor pathways for generating presented peptides directly in the ER, and some evidence suggests that peptides may be further trimmed in this location. The class I heavy chain and beta 2-microglobulin are cotranslationally translocated into the endoplasmic reticulum where their assembly may be facilitated by the sequential association of the heavy chain with chaperone proteins BiP and calnexin. The class I molecule then associates with the lumenal face of TAP where it is retained, presumably awaiting a peptide. After the class I molecule binds a peptide, it is released for exocytosis to the cell surface where cytotoxic T lymphocytes examine it for peptides derived from foreign proteins.

Animals↗

PubMed1997

A complex major histocompatibility complex D locus variant generated by an unusual recombination mechanism in mice.

A spontaneous variant of the mouse class I major histocompatibility complex D(b) gene, designated D(bm28), is characterized. This mutation consists of a cluster of nucleotide substitutions in exon 3 that resembles the product of a classical gene conversion event in that the substituted nucleotides appear to be templated. However, D(bm28) is distinctive, because no single donor gene containing the nucleotide sequence of the mutation exists in the genome of the parent strain. The mutation is consistent with the expected result of an interaction of two donor genes at the target locus during a single recombination event. While no known genetic mechanism gives rise to this class of mutation, we have established that 10 percent of spontaneous class I mutations in the mouse major histocompatibility complex have this complex phenotype. This process occurs at the D locus and the K locus. The significance of this kind of genetic interaction may extend beyond the major histocompatibility complex and have importance in shaping other multigene families.

Animals↗

PubMed1994

The role of major histocompatibility complex and non-major histocompatibility complex encoded antigens in generation of bile duct lesions during hepatic graft-vs.-host responses mediated by helper or cytotoxic T cells.

In these studies, we examined the role of discrete classes of alloantigen differences in generating nonsuppurative cholangitis during graft-vs.-host disease. Transfer of C57BL/6J (B6) splenocytes to class I major histocompatibility complex-disparate bm1 x B6 F1, class II major histocompatibility complex-disparate B6 x bm12 F1, or multiple non-major histocompatibility complex antigen-disparate Balb,B x B6 F1 mice led to the development of periportal inflammatory infiltrates and lymphocyte invasion of bile duct walls. However, frank destruction of bile duct walls was observed only in strain combinations with class I major histocompatibility complex or multiple non-major histocompatibility complex-encoded disparities. The concomitant presence of class II major histocompatibility complex differences and class I major histocompatibility complex or multiple non-major histocompatibility complex differences did not increase and in some cases was associated with less severe bile duct disease than was observed in strain combinations with discrete histocompatibility antigen differences. Depletion of L-leucyl-L-leucine methyl ester-sensitive cytotoxic T lymphocytes from donor inocula reduced the incidence of destructive bile duct lesions observed early in the course of graft-vs.-host disease in B6-->Balb.B x B6 F1 or B6-->bm1 x B6 F1 mice. However, transfer of CD8-negative, L-leucyl-L-leucine methyl ester-resistant T helper cells alone was sufficient to generate destructive cholangitis in class I+II major histocompatibility complex-disparate or multiple non-major histocompatibility complex antigen-disparate strain combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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↗

PubMed1996

Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes.

We present a novel animal model for rheumatoid arthritis induced with a well defined synthetic adjuvant oil, pristane. Two weeks after a single intradermal injection of 150 microliters of pristane, the rats developed severe and chronic arthritis. The inflammation was restricted to the joints and involved pannus formation, major histocompatibility complex (MHC) class II expression, and T lymphocyte infiltration. The initial development as well as the chronic stage of pristane-induced arthritis was ameliorated by treatment with antibodies to the alpha beta-T-cell receptor showing that the disease is T cell dependent. Increased levels of interleukin in serum was seen after pristane injection but not during the chronic stage of arthritis. Joint erosions were accompanied by elevated serum levels of cartilage oligomeric matrix protein. Comparison of MHC congenic LEW strains showed that the severity and chronicity of arthritis varied among the different MHC haplotypes. Rats with RT1f haplotype showed a significantly higher susceptibility to pristane-induced arthritis. A strong influence of non-MHC genes was also suggested by the variability of arthritis susceptibility among different strains with the same MHC haplotype; the most susceptible background was the DA and the least susceptible was the E3. Arthritis induced with a well defined nonimmunogenic adjuvant, with a disease course that closely resembles that of rheumatoid arthritis, makes a suitable animal model for future studies of the pathology and genetics of rheumatoid arthritis.

Animals↗

PubMed1995

Presensitization by skin grafting from major histocompatibility complex class I or major histocompatibility complex class II deficient mice identifies class I antigens as inducers of allosensitization.

Livers but not hearts are accepted spontaneously without immunosuppression when transplanted from B10 (KbAbEbDb) to C3H (KkAkEkDk) mice. Both organs however, undergo accelerated rejection in C3H recipients presensitized with B10 skin grafts. In this study, we have investigated further the role of functional cell-surface major histocompatibility complex (MHC class I or class II molecules in allosensitization. Skin from transgenic MHC class I (b2mmlUncbcr; AbEb) or class II (C2DTM, KbDb) gene 'knockout' mice was grafted onto naive recipients 2-3 weeks prior to whole organ transplantation. When C3H hosts were presensitized with skin from C2DTM (class II deficient) mice, they promptly rejected (within 4 days) subsequently transplanted B10 liver or heart allografts. In contrast, presensitization with skin from b2m (beta 2-m mutant; class I deficient) mice did not significantly affect the survival of either organ graft. Maximal sensitization was established by day 14 after skin grafting and persisted for at least 12 weeks. Splenocytes obtained from C3H mice sensitized with skin from B10, B6 (KbAbEbDb), or C2DTM but not from b2m mice exhibited an H-2b-specific cytolytic response when tested in cell-mediated lymphocytotoxicity assays. Sera from C3H mice sensitized with B10 or b2m skin contained high titres of cytotoxic activity specifically against H-2b class I. Taken together, these observations suggest that in the strain combination studied, MHC class I rather than class II molecules play an important role in allosensitization. The results indicate the potential importance of avoiding transplantation of organs into recipients of secondary grafts from donors that share human leucocyte antigen (HLA) class I antigens with the first donor.

Animals↗

PubMedDate not supplied

Rabbit major histocompatibility complex. IV. Expression of major histocompatibility complex class II genes.

The rabbit MHC class II DP, DQ, and DR alpha and beta chain genes were transfected into murine B lymphoma cells. The transfected cells expressed R-DQ and R-DR molecules on the cell surface but they did not express the R-DP genes either on the cell surface or at the level of mRNA. Northern blot analyses showed that the R-DP genes were expressed, albeit at low levels, in rabbit spleen. Similar analyses showed that the R-DQ and R-DR genes were expressed at high levels in rabbit spleen. A new monoclonal anti-rabbit class II antibody, RDR34, has been developed and shown to react with the R-DR transfected cells and not with the R-DQ transfected cells. The previously described monoclonal anti-rabbit class II antibody, 2C4, reacted with the R-DQ transfected cells and not with the R-DR transfected cells. Thus, 2C4 and RDR34 MAb's are specific for the R-DQ and R-DR molecules, respectively. Each of the antibodies reacted with approximately 50% of rabbit spleen cells as shown by immunofluorescent antibody studies.

Animals↗

PubMed1995

Alloreactive natural killer cells in the rat: complex genetics of major histocompatibility complex control.

A major role for the nonclassical major histocompatibility complex (MHC) class I region, i.e. RT1.C, in controlling rat natural killer (NK) cell alloreactivity has recently been established, and several findings suggested the existence of NK-triggering alloantigens coded for by this region. Here, we have extended our studies on the MHC control of NK cell cytotoxicity against concanavalin A-activated T cell blasts by comparing semi-syngeneic and fully allogeneic combinations, and we show the following: (a) The self MHC exerted a strong influence on the NK allorecognition repertoire. (b) When anti-F1 hybrid cytolytic activities of parental strain NK cells were measured, both recessively and non-recessively inherited susceptibility patterns emerged. (c) In most combinations parental strain cells were lysed by F1 hybrid NK cells, thus resembling the hybrid resistance phenomenon described in mice. The cytotoxicity was lower in strain combinations where NK susceptibility was inherited non-recessively, i.e. when parent anti-F1 reactivity was detected, than in recessive combinations. (d) LEW.1LM1 (RT1lm1) target cells, with a deletion in the RT1.C region that includes expressed class I genes, were more sensitive to lysis by MHC matched NK cells (PVG.1L(LEW), RT1l) than were parental LEW (RT1l) cells. The effect of the deletion was the opposite when MHC allogeneic (RT1c, RT1u) as well as semi-syngeneic (RT1l/c) NK cells were employed, i.e. sensitivity was decreased. We conclude that certain MHC-encoded antigens, depending on the haplotype combination of effector and target cells, may either trigger or inhibit rat NK cell cytotoxicity. Furthermore, the potential role of peptides bound to MHC class I molecules recognized by NK cells is discussed.

Alleles↗

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↗

PubMed1980

Structure and function of major histocompatibility complex.

The major histocompatibility complex (MHC) contains genes that control the structure of many important cell surface antigens and influence a variety of important biological functions. The structures of the MHC in the human, rat and mouse show a remarkable similarity both in terms of the location of their genes and the chemical structures of the gene products. Thus, the region of the chromosome containing the MHC has been highly conserved during evolution, and this finding suggests that its genes are important for survival. Another set of genes, which influences growth and development, is linked to the MHC in the mouse (T/t complex) and in the rat (Grc): this entire chromosomal region may function as a "supergene" with broad effects on tissue organization and compatibility.

Animals↗

PubMed2004

Genetic divergence of the rhesus macaque major histocompatibility complex.

The major histocompatibility complex (MHC) is comprised of the class I, class II, and class III regions, including the MHC class I and class II genes that play a primary role in the immune response and serve as an important model in studies of primate evolution. Although nonhuman primates contribute significantly to comparative human studies, relatively little is known about the genetic diversity and genomics underlying nonhuman primate immunity. To address this issue, we sequenced a complete rhesus macaque MHC spanning over 5.3 Mb, and obtained an additional 2.3 Mb from a second haplotype, including class II and portions of class I and class III. A major expansion of from six class I genes in humans to as many as 22 active MHC class I genes in rhesus and levels of sequence divergence some 10-fold higher than a similar human comparison were found, averaging from 2% to 6% throughout extended portions of class I and class II. These data pose new interpretations of the evolutionary constraints operating between MHC diversity and T-cell selection by contrasting with models predicting an optimal number of antigen presenting genes. For the clinical model, these data and derivative genetic tools can be implemented in ongoing genetic and disease studies that involve the rhesus macaque.

Animals↗

PubMed1989

Genetic characterization of FLA, the cat major histocompatibility complex.

The major histocompatibility complex (MHC) of the domestic cat (termed FLA) has been refractile to genetic and serological definition largely because of repeated failure to detect cytotoxic antibodies in multiparous cats or to elicit antibody following allogeneic lymphocyte immunization. We have developed a protocol for producing cytotoxic alloantisera in the cat following rejection of multiple surgical skin grafts. Of 59 cats subjected to grafting, 13 produced lymphocytotoxic antisera which had varying specificities among a panel of outbred cat cells. A population cluster analysis of the 13 alloantisera permitted the identification of six clusters of overlapping FLA specificities. Serological analysis of cells from 12 cat kindreds led to the definition of 24 allogeneic haplotypes, which segregate as a single Mendelian complex. Feline FLA antisera were characterized as class I or class II specific by immunoprecipitation of FLA gene products on lymphocyte cell surfaces. Abundant antigenic polymorphisms for both class I and class II MHC determinants were discovered, a result consistent with precedence in other species and the common expectation of the adaptive value of MHC variation. Development of feline MHC typing reagents and the definition of haplotypes for the cat hold promise for experimental analysis of valuable feline models for virus-induced immune deficiencies.

Animals↗

PubMed1986

Evolution of the major histocompatibility complex.

The major histocompatibility complex is a group of closely linked loci that code for molecules used by T-lymphocytes as context for the recognition of antigens. The loci fall into two classes: I, coding for molecules used as context by cytotoxic T-lymphocytes and II, used as context by helper and other regulatory T-cells. The Mhc is present in all mammals and perhaps all vertebrates. Some of the Mhc loci are highly polymorphic, while others are not. This article will summarize what is known about the genetic organization of the Mhc in different species and will discuss the selection pressures acting on the individual loci and the tempo and the mechanisms of their evolution.

Animals↗

PubMed1999

The chromosomal duplication model of the major histocompatibility complex.

The major histocompatibility complex (MHC) is a genetic region that has been extensively studied by immunologists, molecular biologists, and evolutionary biologists. Nevertheless, our knowledge of how the MHC acquired its present-day organization is quite limited. The recent discovery that the mammalian genome contains regions paralogous to the MHC has led us to the proposal that the MHC region of jawed vertebrates arose as a result of ancient chromosomal duplications. Here, I review the current status of this proposal.

Animals↗

PubMed1998

Porcine major histocompatibility complex.

The major histocompatibility complex in swine (swine leucocyte antigen: SLA) is located on chromosome 7 with the class I and class III regions separated by the centromere from the class II region. The overall molecular organisation of the class I and III regions is well known, but further research is needed to establish that of the class II region. Approximately sixty genes have been characterised to date, including ten tightly packed SLA class I sequences. The exact number of functional polymorphic class I genes, as defined by serology, probably varies from one to four, depending on the haplotype. At least two other distantly class I-related gene families exist. The numerous and significant associations reported between SLA haplotypes and physiological traits are described. These traits include immune responsiveness to a variety of microbes and metazoan parasites, and male and female production and reproduction performance. The results obtained suggest that selection for specific SLA haplotypes may assist in the improvement of porcine production.

Animals↗

PubMed1993

Composite origin of major histocompatibility complex genes.

Major histocompatibility complex (MHC) genes have now been cloned from representatives of all vertebrate classes except Agnatha. The recent accumulation of sequence data has given great insight into the course of evolution of these genes. Although the primary structure of the MHC genes varies greatly from class to class and also within the individual classes, the general features of the tertiary and quaternary structure have been conserved remarkably well during more than 400 million years of evolution. The ancestral MHC genes may have been assembled from at least three structural elements derived from different gene families. Class II MHC genes appear to have been assembled first, and then to have given rise to class I genes.

Amino Acid Sequence↗

PubMedDate not supplied

The major histocompatibility complex.

The major histocompatibility complex on the sixth chromosome controls expression of a complex series of cell surface antigens which comprise the human leukocyte antigen (HLA) system. These markers, beyond their importance in human organ transplantation, have been demonstrated to occur with an increased prevalence in certain disease states. The group of conditions showing the closest association with specific HLA antigens are the "spondyloarthropathies." These include ankylosing spondylitis (AS), Reiter's syndrome (RS), psoriatic arthritis (PsA), and the arthritis of inflammatory bowel disease (AIBD). Clinical and radiographic studies were made of 310 unrelated caucasoid patients with seronegative arthritis. HLA-A, B, C, and DR typing were performed using the microdroplet lymphocyte cytotoxicity test. Statistically increased prevalences of A26, B27, and Bw38 were observed, while B27 was associated with spinal involvement regardless of diagnosis (90 percent in AS p less than 0.0001). Experiments found A26 (23 percent p less than 0.001) and Bw38 (38 percent p less than 0.0001) in patients with PsA. Spondyloarthritis patients with spinal involvement who lacked B27 frequently had B7. The HLA DR typing for seven specificities was carried out in 196 patients. It was found that DRw4 (52 percent p less than 0.03) and DRw7 (39 percent p less than 0.04) were increased in the PsA patients. This study further confirms the close association of HLA antigens and the spondylarthropathies.

Arthritis↗