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PubMed1996

MHC-associated and MHC-independent urinary chemosignals in mice.

The chemosensory identity of mice, rats, and humans is determined partly by polymorphic genes of the major histocompatibility complex (MHC). In inbred strains of mice as well as in seminatural populations MHC-associated mating preferences selectively influence reproductive success. To explore MHC-associated chemosignals in relation to otherwise genetically determined chemosignals a first study was conducted on seven trained rats' responses to the odors of inbred strains of mice. Results of the first study confirmed that neither the MHC nor genes in the genetic background dominate in determining urine odor specificity of mice and that specific olfactory cues associated with either the MHC or the genetic background can be identified by olfaction. In a second study, these specific olfactory cues were analyzed by means of gas chromatography. The results indicate that specific volatile components associated with either the MHC or the genetic background can be found in mouse urine odor, and that profiles of ubiquitous volatile components show some association with either the MHC or the genetic background. Furthermore, results show that a small number of specific compounds as well as a profile of some few ubiquitous volatiles constitute MHC-associated odor cues and that influences of the MHC and genes in the genetic background interact in constituting urine odor specificity in mice.

Animals↗
PubMed2000

Incomplete penetrance of MHC susceptibility genes: prospective analysis of polygenic MHC-determined traits.

We propose an approach to understanding incomplete penetrance of disease susceptibility genes as a method of studying the underlying mechanisms of polygenic diseases. Incomplete penetrance is the failure of genetically susceptible individuals to exhibit a trait. We define as baseline penetrance that which occurs in genetically identical (monozygotic) twins of an index subject with a major histocompatibility complex (MHC)-associated disease or trait. We consider two mechanisms for incomplete baseline penetrance: an extrinsic (environmental) trigger and an intrinsic stochastic, gene-associated process. The latter can be detected for dominant expression because susceptibility genes in homozygotes (with their two intrinsic triggers) will be up to twice as frequently penetrant as those in heterozygotes. The extent of MHC and non-MHC gene contribution determines differences between baseline penetrance and apparent penetrance in MHC-identical sib pairs, sib pairs in general and MHC-identical unrelated individuals. Inheritance patterns in families do not reveal modes of inheritance of incompletely penetrant polygenic MHC-determined traits. A method is proposed to study such traits prospectively in persons presumed to be homozygous, heterozygous or non-carrying for susceptibility genes by determining trait expression in homozygotes, heterozygotes or non-carriers of trait-associated conserved extended MHC haplotypes. The method provides direct estimates of apparent penetrance rates, modes of genetic determination, and, if the trait is dominant, the origin of penetrance. When applied to dominant MHC susceptibility gene-determined immunoglobulin deficiencies in two populations, the ratios of affected haplotype homozygotes to heterozygotes near 2.0 were consistent with an intrinsic mechanism for baseline penetrance acting on the MHC susceptibility genes.

Environment↗
PubMed1989

Selective decreases in T cell receptor V beta expression. Decreased expression of specific V beta families is associated with expression of multiple MHC and non-MHC gene products.

Previous reports of TCR V beta usage, studying either expression of a single V beta in a wide panel of strains (6, 7, 10, 12, 13), or expression of multiple V beta s in a very limited strain distribution (14, 15), have identified instances of clonal deletion of potentially autoreactive T cells specific for either self E alpha E beta or minor lymphocyte stimulatory (Mls) antigens. The present study has investigated the range of self antigens that can influence V beta usage by evaluating expression of 16 V beta families in 30 strains of mice. It was found that significant decreases in expression occur in at least 8 of the 16 V beta families and that dominant influences on the T cell V beta repertoire are exerted by expression of Mlsa, Mlsc, and MHC gene products. Decreased expressions of V beta 5, -11, -12, and -16 were influenced by MHC gene products. The patterns of decreased expression seen in intra-MHC recombinant strains and strains of different non-MHC background were distinct for V beta 11, -12, and -16, suggesting that different ligands are involved in the deletion of T cells expressing each of these V beta genes. Mice expressing Mlsa show decreased expression of V beta 9 as well as V beta 6. Mlsc mice lacked V beta 3 expression in those strains where the expressed MHC type was compatible with a strongly stimulatory Mlsc phenotype. V beta 7 was strongly influenced by both MHC and non-MHC products that are not yet identified. These results demonstrate that strain-specific decreases of mRNA expression occur in a major portion of the TCR repertoire. Self antigens including Mlsa, Mlsc, and E alpha E beta, as well as additional MHC and non-MHC products, appear to induce these decreases in expression in the process of eliminating self-reactive T cells from the mature T cell pool.

Animals↗
PubMed2004

Cross-linking of MHC class I molecules on human NK cells inhibits NK cell function, segregates MHC I from the NK cell synapse, and induces intracellular phosphotyrosines.

Engagement of major histocompatibility complex (MHC) class I molecules on immune cells, where they are usually highly expressed, induces signal transduction events of unclear significance. We show here that antibody-mediated cross-linking of MHC-I molecules on human natural killer (NK) cells inhibits their cytotoxic activity against tumor target cells. Inhibition by anti-MHC class I monoclonal antibody exhibits molecular specificity and is an isotype and Fc-independent process. Physical hindrance of specific molecular recognition, induction of apoptosis, or reciprocal NK cell killing, which could be induced by cross-linking of MHC I molecules, has also been ruled out as putative mechanisms of inhibition. Confocal microscopy analysis revealed that MHC class I molecules on the surface of NK cells colocalize constitutively with GM1, a marker of lipid rafts. Cross-linking of MHC class I resulted in the asymmetric redistribution of GM1-enriched raft domains, which are concentrated to the immunological synapse, and MHC I molecules, which segregate to the opposite pole. Also, the cross-linking of MHC I on NK cells induced intracellular tyrosine phosphorylations. These results suggest that MHC I molecules on NK cells could transmit inhibitory signals upon engagement with putative ligands expressed on the surface of those cells that need to be protected from natural cytotoxicity.

Antibodies, Monoclonal↗
PubMed2004

17beta-Estradiol inhibits class II major histocompatibility complex (MHC) expression: influence on histone modifications and cbp recruitment to the class II MHC promoter.

Major histocompatibility complex (MHC) class II proteins are important for the initiation of immune responses and are essential for specific recognition of foreign antigens by the immune system. Regulation of class II MHC expression primarily occurs at the transcriptional level. The class II transactivator protein is the master regulator that is essential for both constitutive and interferon-gamma-inducible class II MHC expression. Estrogen [17beta-estradiol (17beta-E2)] has been shown to have immunomodulatory effects. In this study, we show that 17beta-E2 down-regulates interferon-gamma inducible class II MHC protein levels on brain endothelial cells, as well as other cell types (astrocytes, fibrosacroma cells, macrophages). The inhibitory effects of 17beta-E2 on class II MHC expression are not due to changes in class II transactivator mRNA or protein levels, rather, 17beta-E2 mediates inhibition at the level of class II MHC gene expression. We demonstrate that 17beta-E2 attenuates H3 and H4 histone acetylation and cAMP response element binding protein-binding protein association with the class II MHC promoter, suggesting that 17beta-E2 inhibits class II MHC expression by a novel mechanism involving modification of the histone acetylation status of the class II MHC promoter.

Acetylation↗
PubMed2001

Processing of exogenous antigens for presentation by class I MHC molecules involves post-Golgi peptide exchange influenced by peptide-MHC complex stability and acidic pH.

Vacuolar alternate class I MHC (MHC-I) Ag processing allows presentation of exogenous Ag by MHC-I molecules with binding of antigenic peptides to post-Golgi MHC-I molecules. We investigated the role of previously bound peptides and their dissociation in generating peptide-receptive MHC-I molecules. TAP1-knockout macrophages were incubated overnight with an initial exogenous peptide, producing a large cohort of peptide-K(b) complexes that could influence subsequent peptide dissociation/exchange. Initial incubation with FAPGNYPAL, KVVRFDKL, or RGYVYQGL enhanced rather than reduced subsequent binding and presentation of a readout peptide (SIINFEKL or FAPGNYPAL) to T cells. Thus, K(b) molecules may be stabilized by an initial (stabilizing) peptide, enhancing their ability to bind readout peptide and implicating peptide dissociation/exchange. In contrast, incubation with SIINFEKL as stabilizing peptide reduced presentation of readout peptide. SIINFEKL-K(b) complexes were more stable than other peptide-K(b) complexes, which may limit their contribution to peptide exchange. Stabilizing peptides (FAPGNYPAL, KVVRFDKL, or RGYVYQGL) enhanced alternate MHC-I processing of HB101.Crl-OVA (Escherichia coli expressing an OVA fusion protein), indicating that alternate MHC-I Ag processing involves peptide dissociation/exchange. Stabilizing peptide enhanced processing of HB101.Crl-OVA more than presentation of exogenous OVA peptide (SIINFEKL), suggesting that peptide dissociation/exchange may be enhanced in the acidic phagosomal processing environment. Furthermore, exposure of cells to acidic pH increased subsequent binding and presentation of readout peptide. Thus, peptide dissociation/exchange contributes to alternate MHC-I Ag processing and may be influenced by both stability of peptide-MHC-I complexes and pH.

Animals↗
PubMed2001

Cross-linking of MHC class II molecules with anti-MHC class II antibody or epitope peptide prevents resting B lymphocyte differentiation by inhibiting NF-kappaB-dependent gene expression.

To understand the mechanism(s) involved in anti-MHC class II antibody-mediated inhibition of B lymphocyte differentiation, we investigated the influence of anti-MHC class II antibody treatment on the gene expression of IL-6 in resting B lymphocytes, which had been known to be one of the most important cytokines involved in B cell physiology. The level of the IL-6 mRNA expression in the LPS-stimulated resting B cells was remarkably reduced by treatment of the corresponding anti-MHC class II antibodies. The inhibition was exerted in haplotype-specific and dose-dependent manners. Similarly, MHC class II-restricted epitope peptides, when applied as a dimer form, revealed haplotype-specific and dose-dependent inhibitory effects on the IL-6 gene expression by the LPS-stimulated B cells. In addition, treatment of the anti-MHC class II antibody and MHC class II-restricted epitope peptide inhibited, in haplotype-specific and dose-dependent manners, the activation of NF-kappaB, which had been known to be one of the critical transcription factors involved in the IL-6 gene expression. Interestingly, however, exogenous addition of the recombinant IL-6 did not reverse this inhibitory effect by the anti-MHC class II antibody. These results suggest that conjugation of the MHC class II molecules by the anti-MHC class II antibody inhibited B cell differentiation, possibly through the interruption of signaling pathways leading to the IL-6 gene expression via NF-kappaB activation in B lymphocytes.

Animals↗
PubMed1988

Genetic analysis of the presentation of minor lymphocyte stimulating determinants. I. Combined importance of MHC and non-MHC influences.

In the course of studying the MHC restriction of minor lymphocyte stimulating (Mls) determinants, we observed that variation in the ability to present Mlsc determinants occurred with stimulator cells from different mouse strains that express the same class II MHC restricting elements; for example, one Iad-bearing strain, C3H.HTG, presented this non-MHC moiety, whereas another, C3H.OH, could not. As another example, the prototype Mlsb nonstimulatory H-2d stimulator cell, BALB/c, was shown to encode Mlsc even though it failed to trigger proliferation across this non-MHC barrier. In contrast, H-2d-compatible DBA/2 stimulator cells were capable of eliciting detectable levels of unprimed responder T cell proliferation across an Mlsc difference. Even when the BALB/c H-2d haplotype was replaced with the fully permissive H-2K halplotype, these BALB.K stimulator cells presented Mlsc (but not MHC) less effectively than H-2K-compatible C3H/HeJ stimulator cells. Analysis of the Mlsc-presenting capacity of stimulator cells obtained from (BALB.K x C3H) F1 x BALB.K first backcross and (BALB.K x C3H)F2 animals indicated that non-MHC-control influencing stimulatory ability of this non-H-2 Ag was multigenic. In addition, the capacity of DBA/2 to present Mlsa determinants more effectively than MHC-identical LT/ChReSv stimulator cells may indicate that the presentation of this Mls specificity is also influenced by non-MHC Ir genes. Thus the Mls phenotype of an animal should be considered the combined result of an Mls structural gene, the MHC haplotype, and multiple non-H-2 regulatory influences.

Animals↗
PubMed1984

T cell regulation of B cell activation: MHC-restricted T augmenting cells enhance the B cell responses mediated by MHC-restricted cloned T helper cells.

The present studies demonstrated that unprimed populations of Lyt-1+2- T cells are able to augment the responses generated by optimal numbers of antigen-specific and MHC-restricted cloned TH cells. The TA cells function early in the course of B cell responses. Responses mediated by (A X B)F1 (B + accessory) cells and parentA restricted cloned TH cells are augmented by TA cells from (A X B)F1 leads to parentA radiation bone marrow chimeras, but not by TA cells from (A X B)F1 leads to parentB chimeras. Thus, TA cell activation and function are MHC-restricted, but this restriction is not related to recognition of genotypically expressed B cell and/or accessory cell MHC products alone. Rather, TA cell function is intimately related to the MHC-restricted interaction between TH cells and responding (B + accessory) cells. Specifically, it was shown that TH cell interaction with B cells via an MHC-restricted and carrier-hapten-linked pathway is required for the function of TA cells expressing the same MHC restriction. Moreover, neither MHC homology nor TH cell recognition of MHC determinants on TA cells is required for TA cell function, and the activity of TA cells is not demonstrably influenced by non-MHC genes. It was further demonstrated that the function of cloned TH cells in B cell activation consists of at least two distinct components, one is radiosensitive and the other is radioresistant. TA cells are able either to replace the radiosensitive function of cloned TH cells directly or to bypass this requirement through an alternative pathway.

Animals↗
PubMed1984

Induction of T cell differentiation in early-thymectomized Xenopus by grafting adult thymuses from either MHC-matched or from partially or totally MHC-mismatched donors.

The effect of grafting thymuses from major histocompatibility complex (MHC)-matched and mismatched (either partially or totally) adult donors on the restoration of T-cell dependent immune responses of Xenopus adults that were thymectomized (txd) during early larval life was examined. Four to 5 month-old diploid (or triploid) frogs of defined MHC haplotypes that had been txd on day 4 or 5 postfertilization were each grafted subcutaneously with a pair of thymuses from a triploid (or diploid) MHC-defined frog. Regardless of the donor-host combination, thymus grafts restored in vivo acute skin allograft rejection capacities and antibody responses to SRBC and in vitro proliferative responses of spleen cells to the T cell mitogens, PHA and Con A. Txd frogs that were grafted with MHC-mismatched thymus did not reject skin grafts with the MHC haplotype of the thymus donor. Nevertheless, their spleen cells could proliferate, in one way MLC, in response to irradiated stimulator cells with the thymus donor MHC haplotype. Ploidy analyses of mithramycin-stained thymic and splenic lymphocytes (DNA quantitation by flow cytometry) demonstrated that in certain donor-host combinations, cells from totally or partially MHC-mismatched donors as well as from MHC-matched donors persisted in the thymus grafts and/or the spleens of txd hosts. Chimerism lasted for at least 1 year after thymus grafting. In other donor-host combinations, however, (txd isogenic cloned LG15 frogs grafted with allogeneic thymus from MHC-homozygous triploid J strain frogs), no donor cells could be detected 7 months after thymus grafting. Chromosome counts of PHA-induced metaphases of spleen cells from these and other thymus-grafted frogs revealed host cells in metaphase. This suggests that thymus grafts can promote the differentiation of host precursor cells along a T cell pathway.

Animals↗
PubMed1994

MHC class II-bound self-peptides can be effectively separated by isoelectric focusing and bind optimally to their MHC class II restriction elements around pH 5.0.

More than 90% of the major histocompatibility complex (MHC) class II molecules on antigen-presenting cells (APC) have in their binding site a peptide derived from an extracellular protein ingested by the APC or from a protein of the APC itself. These self-peptides can be eluted from affinity-purified MHC class II molecules by acid elution, and have been studied with a variety of techniques. We show here that the self-peptides eluted from the mouse MHC class II molecules Ad, Ed and Ek bind specifically to MHC class II molecules of the allelic type from which they were derived. The pH optimum for binding is around 5.0, i.e. the same optimum at which synthetic peptides representing sequences of foreign antigens bind to MHC class II molecules. This suggests that the physiological compartment where MHC class II molecules bind self-peptides may be very late in the endocytic pathway. The chemical properties of the eluted and labelled MHC class II peptides were studied by isoelectric focusing. This method was able to separate the peptides very efficiently, and enabled a rapid comparison of peptides eluted from different MHC molecules. The 125I-labelled peptides displayed a broad range of isoelectric points with values predominantly below neutral. This suggests that such peptides bind to MHC in a predominantly non-charged state.

Amino Acid Sequence↗
PubMed1997

Alloreactive T cell recognition of MHC class I molecules: the T cell receptor interacts with limited regions of the MHC class I long alpha helices.

T cells recognize MHC-bound peptide, suggesting that the TCR contacts surface MHC residues adjacent to bound peptide, but the extent of MHC contact is not known. T cells also may recognize peptide-induced conformational changes, and alloreactive T cells may recognize surface MHC structures in addition to or independent of bound peptide. Alloreactive T cells are not intentionally biased to recognize particular MHC-bound peptides and should reveal general constraints for TCR binding. To map TCR binding sites, we tested 60 HLA-B7 site-specific mutations with 12 alloreactive CTL clones that express different TCRs. The alloreactive CTL clones recognize solvent-accessible residues that cluster between positions 62 to 80 and 150 to 170. Thus, TCRs contact largely overlapping MHC structures in the alpha1 and alpha2 domain long alpha helices. The dimensions and location of this site are consistent with recently reported crystallographic studies of two TCR/peptide-MHC class I complexes. In contrast to TCR, Abs recognize multiple discrete epitopes that encircle the peptide binding groove and potentially encompass the entire surface of the MHC molecule. Our data suggest that TCRs dock with a common discrete MHC site and that recent crystallographic models are likely to be generally applicable to T cell recognition of peptide-MHC class I complexes.

Amino Acid Sequence↗
PubMed1998

Pig MHC mediates positive selection of mouse CD4+ T cells with a mouse MHC-restricted TCR in pig thymus grafts.

Remarkably normal immune function and specific T cell tolerance to discordant xenogeneic donors can be achieved by grafting fetal pig thymus and liver (FP THY/LIV) tissue to T cell and NK cell-depleted, thymectomized (ATX) mice. To determine whether or not host class II MHC molecules participate in the positive selection of mouse CD4+ T cells in FP THY/LIV grafts, we compared their development in ATX "AND" TCR-transgenic mice with positive selecting or nonselecting host MHC genotypes. Mouse TCR-transgenic CD4 single positive T cells repopulated the periphery significantly and to a similar extent in both T/NK cell-depleted, ATX AND mice with positive-selecting or nonselecting MHC backgrounds after grafting with FP THY/LIV. Therefore, MHC molecules from a widely disparate xenogeneic species can positively select T cells bearing a host class II MHC-restricted TCR without a contribution from the host MHC. These results, in combination with previous studies performed in this model, suggest that the T cell repertoire that is generated by the combination of positive selection on xenogeneic MHC and negative selection on both recipient and xenogeneic porcine MHC is tolerant of both donor and recipient and has sufficient cross-reactivity with host MHC/foreign peptide complexes to confer a high level of immunocompetence. The results have implications for the potential clinical applicability of xenogeneic thymic transplantation and also suggest a predominant role for the TCR recognition of species-conserved MHC residues in positive selection.

Animals↗
PubMed1995

Selective expression of major histocompatibility complex (MHC) antigens and modulation of T-cell differentiation in chickens with increased MHC-chromosome dosages.

Increased dosage of genes belonging to the immunoglobulin superfamily may be responsible for some of the less noticeable but targeted phenotypic disturbances seen in trisomy conditions of humans and animals. We used an avian aneuploidy model to study the specific effects of extra major histocompatibility complex (MHC)-microchromosome dosage on the progression of thymocyte differentiation through a broad period of embryonic and neonatal development. The particular goal in the present investigation was to determine whether a reduction in the number of thymocytes, previously observed in the developing thymus of MHC aneuploids, is accompanied by particular alterations in thymocyte differentiation. We hypothesized that the subpopulation structure and/or developmental pattern for thymocyte differentiation are characteristically perturbed (delayed or modified) by increased MHC-chromosome dosage in cells. The regulation of MHC surface antigen expression in aneuploid thymocytes was also studied to detect dosage-dependent expression for one and possibly more sub-regions (class I, II, IV) of the avian MHC. Surface densities of MHC class I antigens on thymocytes were increased significantly at all ages studied, for example by 15% and 45% in trisomics and tetrasomics, respectively at 22 days post-hatching. The surface density of CT1 antigen, a thymocyte-specific marker, was also increased in a dosage-dependent manner, but only in juveniles. Increases in the proportion of alpha beta 1, TCR+ and CD3+ thymocytes were observed in juveniles, with no alterations in other TCR-expressing thymocytes. No major alterations in CD4 and CD8 thymocyte populations were observed. These results demonstrate a targeted effect of extra MHC-chromosome dosage towards enhanced class I and CT1, and not class II or IV, expression. The increased MHC-microchromosome dosage appears to influence primarily immature thymocytes expressing alpha beta 1 TCR and CD3.

Aneuploidy↗
PubMed1989

The combination of major histocompatibility complex (MHC) and non-MHC genes influences murine lymphocytic choriomeningitis virus pathogenesis.

Resistance to the acute lethal disease caused by the docile strain of lymphocytic choriomeningitis (LCM) virus varies widely between different mouse strains. In order to study the inheritance of host influence on susceptibility to this strain of LCM virus, we crossed the F1 to the parent with the recessive disease phenotype. In all cases, susceptibility was dominant. In backcross progeny obtained from matings of parental strains differing in both major histocompatibility complex (MHC) and non-MHC (SWR; C3H), 90% of the challenged mice died, indicating that at least three loci controlled susceptibility to the disease. When the parental strains carried similar MHC haplotypes but dissimilar background genes (B10.BR; CBA), 78% of the backcross mice succumbed, indicating that at least two non-MHC loci influenced disease susceptibility. It is unlikely, however, that the same two non-MHC loci are critical in all genetic combinations, since F1 produced from two H-2 identical, resistant strains (B10.BR; C3H) were found to be fully susceptible. When congenic mice, differing only in the D-end of the MHC region, were analysed, 50% of the backcross animals died, indicating that one gene in the MHC region was important; segregation analysis comparing MHC serotype and disease outcome indicated the H-2D locus itself as the determining factor.

Animals↗
PubMed2000

Increased major histocompatibility complex (MHC) expression in nontoxic goiters is associated with iodide depletion, enhanced ability of the follicular thyroglobulin to increase MHC gene expression, and thyroid autoantibodies.

Recent studies suggest that thyroglobulin (TG) accumulated in the follicular lumen of colloid nodular goiters can increase major histocompatibility complex (MHC) class I gene expression in FRTL-5 thyrocytes. Iodide deficiency, also present in these patients, was separately suggested to enhance thyroidal MHC class I and class II gene expression in vivo and in vitro. To test the clinical relevance of these observations, we examined 41 nontoxic goiters surgically removed from patients who had compression problems. Northern analysis revealed that there was a mean 3.9-fold increase in MHC class I expression and a 8.3-fold increase in class II expression by comparison to 9 normal glands. In situ hybridization showed that thyrocytes were the main source of class I and class II transcripts; histological examination revealed that lymphocytic infiltration was minimal to non-existent. The iodine content of the 41 nontoxic goiters was significantly lower than in normal glands, consistent with increased MHC class I and class II. There is also a profound accumulation of TG in the follicles of the nontoxic goiters, and TG purified from the follicles of these glands increased MHC class I gene expression in FRTL-5 thyroid cells significantly more than TG from normal glands per mg protein. Nearly all patients with nontoxic goiter had low, but significantly elevated, levels of antibodies against thyroid peroxidase and/or against TG in their sera compared with those in normal individuals. Moreover, there was a positive correlation between the titer of the serum antibodies against thyroid peroxidase and against TG and MHC class I and class II expression in the thyroid. The data support the possibility that the TG accumulated in the follicular lumen of nontoxic goiters together with relative iodine deficiency contributes to increased MHC expression in thyroid cells in vivo and that increased MHC gene expression contributes to the ability of thyroid antigens to trigger an autoimmune reaction.

Adult↗
PubMed1999

Transcriptional control of MHC genes and T cell development in MHC class II deficiency.

MHC class II deficiency has proven to be an excellent model to study transcription regulation of MHC genes and T cell development. Cell lines established from MHC class II deficient patients have been of great value for the identification of proteins necessary for MHC expression and their study has resulted in the identification of a common regulatory pathway for MHC class II and class I genes. The lack of MHC class II expression was found to have a profound effect on the development of the CD4+ T cell lineage, in particular on the composition of the T cell receptor repertoire, revealing aberrant thymic selection processes in these patients. Here, we will discuss several aspects of the transcriptional regulation of MHC genes and the impact of deficient MHC class II expression on T cell development.

CD4-Positive T-Lymphocytes↗
PubMed1996

The MHC class I genes of the rhesus monkey. Different evolutionary histories of MHC class I and II genes in primates.

Homologues of the human HLA-A and -B MHC class I loci have been found in great apes and Old World primates suggesting that these two loci have existed for at least 30 million years. The C locus, however, shows some sequence similarity to the B locus and has been found only in gorillas, chimpanzees, and humans. To determine the age of the MHC class I C locus and to examine the evolution of the A and B loci we have cloned, sequenced, and in vitro translated 16 MHC class I cDNAs from two unrelated rhesus monkeys (Macaca mulatta) using both cDNA library screening and PCR amplification. Analyses of these sequences suggest that the C locus is not present in the rhesus monkey, indicating that this locus may be of recent origin in gorillas, chimpanzees, and humans. The rhesus monkey's complement of MHC class I genes includes the products of at least one expressed A locus and at least two expressed B loci, indicating that a duplication of the B locus has taken place in the lineage leading to these Old World primates. Comparison of rhesus monkey MHC class I cDNAs to their primate counterparts reveals fundamental differences between MHC class I and class II evolution in primates. Although MHC class II allelic lineages are shared between humans and Old World primates, no such trans-species sharing of allelic lineages is seen at the MHC class I loci.

Animals↗