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Results for “major histocompatibility complex”

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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↗
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↗
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↗
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↗
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↗
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↗
PubMed1976

Genetics of transplantation: the major histocompatibility complex.

A genetic region called the major histocompatibility complex of MHC (which plays an important role in the control of graft survival) has been defined in a large number of different species. Several different loci of the MHC have been described, including loci coding for transplantation antigens. These antigens can be divided into two categories: first, the SD antigens that were originally defined serologically and that appear to function as targets for the killer lymphocytes involved in the rejection of a graft and second, the LD antigens that were originally defined by lymphocyte response in the mixed leukocyte culture test and that stimulate helper T lymphocytes. In addition, there are genes for other antigens (referred to as immune response-associated or Ia antigens) and genes that control the ability of an animal to respond immunologically to antigenic stimuli, the immune response or Ir genes. There is evidence for epistatic interaction between these genes in that immune recognition of LD and SD antigens lead to a more pronounced development of cytotoxic (killer) cells than does stimulation by either antigen alone. In addition, the genetic control of immune responsiveness appears, at least in some systems, to reside in two very closely linked genes that may function better in the cis than in the transposition. This latter finding suggests a possible explanation for the strong linkage disequilibrium found between genes of the MHC. A number of new tests have been described to define the antigens of the MHC. Results of these tests have been used for studies of transplantation immunology but in addition to study the very strong associations that exist between some of the MHC antigens in man and various diseases.

Antibody Formation↗
PubMed1976

Differential cellular immune responsiveness to systems of the major histocompatibility complex.

Antigens determined by genes of the major histocompatibility complex can be divided into two systems" the LD (lymphocyte-defined or L determinant) and SD (serologically defined or S determinant) antigens. This division is based on the differential cellular responsiveness to these two sets of antigens of two subpopulations of T lymphocytes: a proliferating helper cell responds primarily to the LD antigens while a cytotoxic T lymphocyte responds most strongly to the SD antigens.

Animals↗
PubMed1979

The influence of the major histocompatibility complex (H-2) on experimental diabetes in mice.

Mice with different histocompatibility loci on an identical background genome (congenic resistant lines of mice) were used to study the possible influence of the histocompatibility complex on experimental diabetes. The major histocompatibility complex (H-2) was not found to influence the diabetogenic effect of encephalomyocarditis (EMC) virus. In contrast the glucose intolerance following heterologous and homologous immunization with pancreatic antigens appeared H-2 influenced. Antibodies against cell surface components on viable B-cells were present in serum from mice with glucose intolerance induced by homologous immunization. The results suggest that the susceptibility to experimental autoimmune diabetes in mice is influenced by the H-2 complex.

Animals↗
PubMedDate not supplied

[Biological and evolutionary significance of the major histocompatibility complex].

The recent advances in the understanding of the Major Histocompatibility Complex, particularly of human HLA and murine H2, are critically reviewed. Special emphasis has been given to the new hypotheses regarding MHC a "rejection" system for recognizing and eliminating cells that have been altered in the expression of their so called transplantation antigens by viral infection or oncogenic transformation. Because Ir genes are certainly involved in controlling the immune response against modified autologous MHC antigens, the author forwards an original hypothesis for explaining the linkage disequilibrium between different alleles at the HLA: A, B, C loci: the Ir gene (genes) in a given haplotype is particularly efficient for recognizing some particular altered antigens of different serie (say A1 and B8; A3 and B7). If these is the case the Ir gene (genes) would be the Keystone for maintaining the preferential associations of some pseudoalleles in some haplotypes.

Alleles↗
PubMed1979

Genetics of kidney allograft survival in dogs. I. Relevance of subregions of the major histocompatibility complex in recipients without immunosuppressive therapy.

The influence of subregions of the canine major histocompatibility complex (MHC) on renal allograft survival is assessed in recipients without immunosuppressive therapy. Results in six beagle littermate donor-recipient pairs in which the donor or recipient had a recombination in the MHC are compatible with the concept of a predominant role for the subregion containing the major mixed lymphocyte reaction (MLR) locus in determining allograft survival. Results in unrelated mongrel dogs indicate that compatibility for MLR induces a longer kidney allograft survival than compatibility for the serologically defined (SD) antigens. However, the effect of combined matching for MLR and SD antigens in unrelated donor-recipient pairs is slight in comparison to the effect of MLR and/or SD matching in littermate-related dogs. This indicates that other important histocompatibility systems probably exist in this species.

Animals↗
PubMed1976

Products of the major histocompatibility complex and their relationship to the immune response.

The genes of the major histocompatibility complex were first known for the part they played in transplant rejection. Recently, however, it has become clear that the products of that region have an important part to play in the control of the immune response, through their effects both on cooperative and on aggressive interactions between cells. It is now possible to guess at the mechanisms which may underly the association of some major histocompatibility antigens with disease.

Alleles↗
PubMed1978

At least two loci of the major histocompatibility complex can determine mixed lymphocyte stimulation in the rat.

Analysis of a recombinant haplotype of the major histocompatibility complex showed that two genetically separable loci (or groups of loci), LD--1 and LD--2, determine mixed lymphocyte stimulation in the rat. LD--1 maps into the H--1B region which contains the Ir genes and is associated with strong, mixed lymphocyte stimulation. LD--2 maps into the H--1A region and determines weak stimulation. LD--1 and LD--2 determinants can be detected by primed lymphocyte typing.

Animals↗
PubMed1976

T cell-specific human alloantisera-detecting antigens segregating outside the major histocompatibility complex.

Two sera demonstrated non-HLA lymphocytotoxicity on the basis of reactivity with the cells of siblings genotypically identical to the serum donors for the major histocompatibility complex. These two sera, Bl and Caf, once contaminating HLA antibodies were removed by absorption with pooled platelets, demonstrated allogeneic lymphocytotoxicity that was restricted to T lymphocytes. Reactivity of the absorbed sera segregated independently of the major histocompatibility complex in 3 of 12 families tested. Unlike both cold lymphotoxins and HLA antibodies, the absorbed sera showed little temperature sensitivity against allogeneic cells, although reactivity of the Bl serum to autologous cells and to cells of the donor's HLA identical sibling did show a decrease with increasing temperature and restriction of activity to the 19S-containing fraction. Granulocytes were unreactive with the absorbed sera. Such sera may provide probes of minor transplantation antigens or markers, or both, of lymphoid subpopulations.

Adult↗
PubMed1978

Serological studies on the major histocompatibility complex of new inbred strains of the guinea pig.

New inbred strains of guinea pigs, JY 1, JY 2, JY 3, JY 6, JY 9 and JY 10 have been established in this Institute. Serologic studies of guinea pig leukocyte antigens (GPLA antigens) were carried out in order to examine their major histocompatibility complex (GPLA complex). Antisera specific for Ia antigens were raised by cross-immunization of NIH strain 2 (NIH 2) and NIH strain 13 (NIH 13) guinea pigs, well known inbred guinea pigs. The sera identified four distinct Ia specificities, which were designated as Ia.2a, Ia2b, Ia.13a and Ia.13b. Six antigenic specificities different from the above Ia specificities were identified by sera obtained by appropriate immunization of the inbred guinea pigs and were designated as P.1, P.2, P.3, P.4, P.5 and P.6. Antigenic specificities of GPLA antigens recognized in inbred guinea pigs were : NIH 2 (Ia.2a, Ia.2b, P.1, P.2, P.O, P.4), NIH 13 (Ia.13a, Ia.13b, P.1, P.2, P.3, P.4), JY 1 (Ia.13a, Ia.13b, P.5), JY 2 (Ia.2b, Ia.13b, P.3, P.4, P.6), JY 3 (Ia.13a, Ia.13b, P.2, P.4, P.5), JY 6 (Ia.2b, Ia.13b, P.3, P.6), JY 9 (Ia.13a, Ia.13b, P.4, P.5), JY 10 (Ia.13a, Ia.13b, P.2, P.3, P.4, P.6), JY 9 (Ia.13a, Ia.13b, P.4, P.5), JY 10 (Ia.13a, Ia.13b, P.2, P.3, P.4, P.6). The correspondence of these specificities to those already reported was discussed and the P.2 or P.4 was considered to be an additional specificity of GPLA antigens that have not been reported yet. As the new inbred strains of guinea pigs were thus found to possess characteristic GPLA complex, which differ from each other and from those of NIH 2 and NIH 13 strain, they should be useful for studies of roles of the major histocompatibility complex in the immune system.

Animals↗
PubMed1976

Recognitive specificity of human cytotoxic T lymphocytes. II. The non-recognition of antigens controlled outside the major histocompatibility complex.

In vitro sensitized cytotoxic T lymphocytes (CTLs) primarily detect antigens controlled within the major histocompatibility complex (MHC) that are associated with the serologically detected (SD) loci LA and FOUR. Frequently CTLs sensitized to cells from one individual kill target cells of a third party that shares no SD cross-reactivities by serological criteria with the initial stimulating cells. We have studied the possibility that this cross-killing is due to the recognition of non-MHC controlled antigens. Allogeneic tissue from MHC identical siblings is rejected in the absence of immunosuppression, demonstrating the importance of non-MHC antigens. Nevertheless, CTLs sensitized simultaneously with mitomycin-C treated cells from an MHC identical sibling and from an unrelated individual were only able to mediate cytotoxicity on the unrelated's target cells. No significant cytotoxicity was observed in any combination on target cells differing only for non-MHC antigens.

Consanguinity↗
PubMed1976

Evidence for more than one Ia antigenic specificity on molecules determined by the I-A subregion of the mouse major histocompatibility complex.

Ia antigenic specificities determined by the I-A subregion of the mouse major histocompatibility complex have been examined in strain B10.D2 (H-2d), C57BL/10 (H-2b), and in a (C57BL/6xDBA/2) hybrid (BDF1; H-2b/d). Detergent solubilized, 3H-leucine-labeled antigen preparations were mixed with appropriate alloantisera and precipitation was induced either by addition of goat anti-mouse gamma-globulin or by addition of protein A-bearing Staphylococci. Sequential precipitation analysis showed that in strain B10.D2, Ia specificities 8 and 11 were co-precipitable, and that in strain C57BL/10, Ia specificities 8 and 9 were co-precipitable. In contrast, precipitation of specificities 9 and 11 from a BDF1 antigen preparation showed that these two Ia specificities were on separate molecules. The genetic implications of these data are discussed.

Animals↗
PubMed1978

Primary structure of murine major histocompatibility complex alloantigens: amino acid sequence studies of the cyanogen bromide fragments of the H-2Kb glycoprotein.

Radiochemical microtechniques have been used in the amino acid sequence analysis of five major CNBr fragments of the glycoprotein specified by the murine major histocompatibility complex gene H-2k(b). These fragments have been tentatively aligned and represent the NH(2)-terminal 80% of the intact molecule. All amino acids except Asp, Asn, and Gln have been assigned in 128 out of 149 possible positions in the NH(2)-terminal portions of each of these fragments. These assignments, which represent approximately 50% of the total sequence from these fragments, are listed below in the order of their alignment in the intact H-2K(b) molecule: IIIn, -PHSLRYFVTAVSRP(G)L(G)(E)PRYM; IIIa, EVGYV--TEFVRF-S-AE(A)PRYEPR(A)--M; Ib, E-EGPEYWERET-KAK(G)-E-SFR--LRTLL(G)YY--TK; Ia, AALITK-KWE-AGEAERLRAYLEGTC-E-L; Ic, ELVETRPAG-GTF-KWAS-VVPLGKE-YY(T). The unassigned positions represented by dashes in the above sequences may be tentatively assigned as Asp, Asn, or Gln. The NH(2)-terminal sequence obtained for the H-2K(b) molecule was compared to the limited sequence information available for other major histocompatibility complex gene products. An 84% homology (16 of 19 residues) to the H-2K(q) and H-2K(k) molecules, which are identical to one another in the positions compared, was observed. A similar comparison with 28 of the 31 NH(2)-terminal residues of HLA-B7 indicated 68% homology. Furthermore, significant homology was observed between H-K(b) and HLA-B7 in a region of glycosylation, which occurs between positions 85 and 100 in the two molecules.

Amino Acid Sequence↗