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PubMed2000

Effects of spaceflight and thyroid deficiency on rat hindlimb development. II. Expression of MHC isoforms.

Both slow-twitch and fast-twitch muscles are undifferentiated after birth as to their contractile protein phenotype. Thus we examined the separate and combined effects of spaceflight (SF) and thyroid deficiency (TD) on myosin heavy chain (MHC) gene expression (protein and mRNA) in muscles of neonatal rats (7 and 14 days of age at launch) exposed to SF for 16 days. Spaceflight markedly reduced expression of the slow, type I MHC gene by approximately 55%, whereas it augmented expression of the fast IIx and IIb MHCs in antigravity skeletal muscles. In fast muscles, SF caused subtle increases in the fast IIb MHC relative to the other adult MHCs. In contrast, TD prevented the normal expression of the fast MHC phenotype, particularly the IIb MHC, whereas TD maintained expression of the embryonic/neonatal MHC isoforms; this response occurred independently of gravity. Collectively, these results suggest that normal expression of the type I MHC gene requires signals associated with weight-bearing activity, whereas normal expression of the IIb MHC requires an intact thyroid state acting independently of the weight-bearing activities typically encountered during neonatal development of laboratory rodents. Finally, MHC expression in developing muscles is chiefly regulated by pretranslational processes based on the tight relationship between the MHC protein and mRNA data.

Animals↗
PubMed2006

Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage.

Several studies indicate that cell-mediated immune responses, i.e., macrophage (MPhi) cytokine release capacities, myosin heavy chain (MHC) class II (Ia) expression, etc., are suppressed after trauma-hemorrhage in male mice. Testosterone has been shown to be responsible for the depression of MPhi cytokine responses in males after trauma-hemorrhage. Antigen presentation via MHC class II plays a key role in initiating and maintaining cell-mediated and humoral immune responses. It remains unknown, however, whether testosterone has any effect on MHC class II after trauma-hemorrhage. To study this, male C3H/HeN mice were castrated or sham castrated 2 wk before trauma (midline laparotomy) and hemorrhage (Hem; blood pressure 35 +/- 5 mmHg for 90 min and resuscitation) or sham operation. Four hours thereafter, MHC class II (Ia) expression was measured using flow cytometry. The results indicate that MHC class II (Ia) expression on peritoneal and splenic MPhi was significantly suppressed in male mice after trauma-hemorrhage. Prior castration, however, prevented the depression in MHC class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage. Castration did not affect MHC class II (Ia) expression in MPhi from sham-castrated mice. Thus testosterone depresses MHC class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage in males. Because MHC class II is necessary for an adequate immune response, our results suggest that depletion of male sex steroids or blockade of androgen receptors using agents such as flutamide might prevent immunosuppression via maintaining MHC class II (Ia) expression after trauma and severe blood loss.

Androgen Antagonists↗
PubMed2001

A geometric and algebraic view of MHC-peptide complexes and their binding properties.

BACKGROUND: Major histocompatibility complex (MHC) molecules present peptides to T lymphocytes. It is of critical biological and medical importance to elucidate how different MHC alleles bind to a specific set of peptides. METHOD: In this study we approach the problem from the algebraic and geometric point of view to analyse MHC-peptide-binding data accumulated over the years. The space of sequence properties (having a particular amino acid at a particular position) of MHC-peptide complexes conveys a geometric structure to these sequence properties in the form of a distance measure, which reveals the peptide binding requirements imposed by the polymorphic sequence characteristics of the MHC molecules. RESULTS: Comparison of the results of this study with our current knowledge of MHC-peptide binding constraints leads to robust agreement. This study provides the tools to quantitate these binding constraints giving a more detailed account of them and opening the way to make peptide binding predictions for MHC alleles for which there is no peptide elution data. In addition, the geometric representation of MHC-peptide complex sequence data gives a distance measure between amino acids in reference to their ability to meet MHC binding requirements. CONCLUSIONS: The algebraic and geometric view of amino acid sequences provides a theoretical framework to study the function of proteins when there is enough variation in this sequence to account for the variation in their function, as it is the case with MHC molecules in regard to their ability to present peptides.

Alleles↗
PubMed1990

Strain-specific determination of the degree of thyroid cell MHC class II antigen expression: evaluation of established Wistar and Fisher rat thyroid cell lines.

The major histocompatibility complex (MHC) genes, primarily of the MHC class II region, are linked to increased susceptibility to autoimmune thyroid disease in animals and humans. The quantity of MHC class II antigens that are expressed on the appropriate cell surface, as well as their allotype, are of vital importance to immune function. We have, therefore, compared MHC class II (RT1.D) gene activation in a newly available Wistar rat thyroid (WRT) cell line (a thyroiditis-susceptible strain) with a cloned cell (1B-6) derived from the Fisher rat thyroid cell line (FRTL-5) (a thyroiditis-resistant strain) to determine differences in their degree of MHC class II gene activation and antigen expression. There was no detectable constitutive MHC class II antigen or RT1.D alpha-chain messenger RNA expression in either WRT or 1B-6 cells. Cultures of both cells expressed MHC class II gene induction in response to recombinant rat gamma-interferon (gamma IF). After 72 h of exposure to 25 U/ml gamma IF, over 80% of WRT cells expressed class II antigen, detected by flow cytometric assessment, as compared to only 15% of 1B-6 cells. This earlier and greater expression of MHC class II antigen was reflected in the RT1.D alpha-chain mRNA responses with peak levels in WRT cells after only 24 h of exposure to gamma IF, a period in which 1B-6 cells showed only minor increases in mRNA. To examine whether these differences in class II MHC expression were thyroid-cell specific, primary pulmonary fibroblast lines from Wistar and Fisher rats were developed and a similar, although less marked, variation in susceptibility to gamma IF was observed. Hence, those rats strains that are resistant to autoimmune thyroid disease exhibit a fundamental difference in their MHC class II gene responsiveness to cytokines, which may contribute to their disease susceptibility profiles.

Animals↗
PubMed1988

Regulation of MHC protein expression in pancreatic beta-cells by interferon-gamma and tumor necrosis factor-alpha.

Isolated human and mouse pancreatic islet cells and the rat insulinoma cell line RIN-m5F were used to examine the ability of recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) to regulate the expression of the class I and class II major histocompatibility (MHC) surface proteins and mRNA in beta-cells. Each cytokine increased significantly the expression of class I MHC proteins as determined by double indirect immunofluorescence microscopy and flow cytofluorimetric analysis. In the RIN-m5F cells, this increase in surface expressed class I MHC proteins was mirrored by an increase in the level of class I MHC mRNA. The order of potency of the cytokines on class I MHC expression was TNF-alpha plus IFN-gamma greater than or equal to IFN-gamma greater than or equal to TNF-alpha. While IFN-gamma or TNF-alpha alone were without effect, in combination they were found to induce class II MHC proteins on 30-40% of human or murine beta-cells. In contrast, IFN-gamma plus TNF-alpha did not induce detectable class II MHC proteins or mRNA in the RIN-m5F cells. These findings indicate that 1) TNF-alpha, in addition to IFN-gamma, upregulates the expression of beta-cell class I MHC proteins and mRNA, and 2) more than one signal is required for the induction of class II MHC proteins on beta-cells. The ability of IFN-gamma plus TNF-alpha to induce class II MHC proteins on only a fraction of the normal beta-cell population and not on RIN-m5F cells suggests that this response is related to the differentiation state of the beta-cell.

Animals↗
PubMed2000

Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and induces their apoptosis.

Infection by Helicobacter pylori leads to injury of the gastric epithelium and a cellular infiltrate that includes CD4+ T cells. H. pylori binds to class II MHC molecules on gastric epithelial cells and induces their apoptosis. Because urease is an abundant protein expressed by H. pylori, we examined whether it had the ability to bind class II MHC and induce apoptosis in class II MHC-bearing cells. Flow cytometry revealed the binding of PE-conjugated urease to class II MHC+ gastric epithelial cell lines. The binding of urease to human gastric epithelial cells was reduced by anti-class II MHC Abs and by staphylococcal enterotoxin B. The binding of urease to class II MHC was confirmed when urease bound to HLA-DR1-transfected COS-1 (1D12) cells but not to untransfected COS-1 cells. Urease also bound to a panel of B cell lines expressing various class II MHC alleles. Recombinant urease induced apoptosis in gastric epithelial cells that express class II MHC molecules, but not in class II MHC- cells. Also, Fab from anti-class II MHC and not from isotype control Abs blocked the induction of apoptosis by urease in a concentration-dependent manner. The adhesin properties of urease might point to a novel and important role of H. pylori urease in the pathogenesis of H. pylori infection.

Alleles↗
PubMed2004

MHC class II molecules traffic into lipid rafts during intracellular transport.

There have been many studies demonstrating that a portion of MHC class II molecules reside in detergent-insoluble membrane domains (commonly referred to as lipid rafts). We have proposed that the function of raft association is to concentrate specific MHC class II-peptide complexes in plasma membrane microdomains that can facilitate efficient T cell activation. We now show that MHC class II becomes lipid raft associated before binding antigenic peptides. Using pulse-chase radiolabeling techniques, we find that newly synthesized MHC class II and MHC class II-invariant chain complexes initially reside in a detergent-soluble membrane fraction and acquire detergent insolubility as they traffic to lysosomal Ag processing compartments. Monensin, an inhibitor of protein transport through the Golgi apparatus, blocks association of newly synthesized MHC class II with lipid rafts. Treatment of cells with leupeptin, which inhibits invariant chain degradation, leads to the accumulation of MHC class II in lipid rafts within the lysosome-like Ag-processing compartments. Raft fractionation of lysosomal membranes confirmed the presence of MHC class II in detergent-insoluble microdomains in Ag-processing compartments. These findings indicate that newly synthesized MHC class II complexes are directed to detergent-insoluble lipid raft microdomains before peptide loading, a process that may facilitate the loading of similar peptides on MHC class II complexes in these microdomains.

Antigen Presentation↗
PubMed2006

Tumor-specific CD4+ T cells are activated by "cross-dressed" dendritic cells presenting peptide-MHC class II complexes acquired from cell-based cancer vaccines.

Tumor cells that constitutively express MHC class I molecules and are genetically modified to express MHC class II (MHC II) and costimulatory molecules are immunogenic and have therapeutic efficacy against established primary and metastatic cancers in syngeneic mice and activate tumor-specific human CD4+ T lymphocytes. Previous studies have indicated that these MHC II vaccines enhance immunity by directly activating tumor-specific CD4+ T cells during the immunization process. Because dendritic cells (DCs) are considered to be the most efficient APCs, we have now examined the role of DCs in CD4+ T cell activation by the MHC II vaccines. Surprisingly, we find that DCs are essential for MHC II vaccine immunogenicity; however, they mediate their effect through "cross-dressing." Cross-dressing, or peptide-MHC (pMHC) transfer, involves the generation of pMHC complexes within the vaccine cells, and their subsequent transfer to DCs, which then present the intact, unprocessed complexes to CD4+ T lymphocytes. The net result is that DCs are the functional APCs; however, the immunogenic pMHC complexes are generated by the tumor cells. Because MHC II vaccine cells do not express the MHC II accessory molecules invariant chain and DM, they are likely to load additional tumor Ag epitopes onto MHC II molecules and therefore activate a different repertoire of T cells than DCs. These data further the concept that transfer of cellular material to DCs is important in Ag presentation, and they have direct implications for the design of cancer vaccines.

Animals↗
PubMed1986

Ontogeny of MHC-linked, T cell-mediated suppression is regulated by the T cell genotype.

Regulation of T cell effector functions by major histocompatibility complex (MHC) gene products has been extensively researched. Investigations in this area have established several important concepts of immunobiology. First, genes within the I-region of the MHC profoundly affect development of immune responses through their effects on cell-cell interactions. In the course of analyzing antigen-induced T cell activation, investigators identified specific Ir-genes by demonstrating that certain strains of mice were unable to develop immunity to defined antigens. It is now accepted that immune response defects in murine species are potentiated by cell surface molecules encoded within the I-subregion of the MHC, called Ia. Those molecules coded within the I-A subregion have the potential to be expressed by many different cell types. Second, induction of helper T cell effector function requires recognition of antigen in association with I-region encoded, cell surface molecules. For example, only a single structural combination of antigenic determinant and Ia molecule can deliver the inductive signal(s) to potential helper T cells. This fundamental aspect of helper T cell activation, now documented in numerous experimental systems, is referred to as MHC- or I-region restricted, antigen recognition. MHC-restriction is a characteristic of T cells mediating delayed-type hypersensitivity, help, and cytotoxicity. Third, several lines of evidence have established that T cell recognition of self-MHC molecules is a modifiable phenotype; conferred by a receptor having both variable and constant regions and not encoded by genes in the MHC. The development of both thymic grafted homozygous nu/nu mice and irradiation-induced bone marrow chimeras as experimental models resulted in a better understanding of the mechanism of MHC-restricted, antigen recognition. It was observed that expression of MHC gene products by the host is sufficient to select a new immune response phenotype for cellular interactions. The selection process takes place during T cell maturation, in the absence of antigen and under the dominant influence of the thymus, even though there is ample evidence for selective pressure in the extrathymic environment. For example, the self-MHC recognition repertoire of T cells in P----F1 chimeras undergoes an initial expansion which results in an F1 immune response phenotype. This expansion is followed by an apparent contraction back to the immune response phenotype of the parental donor. The contraction is time dependent and reflects accessory cell turnover in the irradiated host.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Activation of MHC-restricted rat T cells by cloned syngeneic thyrocytes.

We have previously demonstrated that rat thyrocytes express MHC class II Ag (RT1.B&D) in response to IFN-gamma. To determine whether MHC class II-positive thyrocytes can be recognized by MHC-restricted T cells, we used our clone of rat thyroid cells (1B-6) derived from the Fisher rat thyroid cell line (FRTL-5) and known to express MHC class II Ag in response to recombinant rat IFN-gamma. CD4+ and CD8+ normal syngeneic Fisher rat spleen T cells were selected by flow cytometry and averaged greater than 96% purity. We demonstrated that irradiated MHC class II-positive but not class II-negative 1B-6 thyrocytes stimulated CD4+ T cells in a primary sensitization reaction over 4 days. In contrast, CD8+ T cells had no response in similar experiments. This stimulation of CD4+ T cells was dose dependent for 1B-6 thyrocytes and was abrogated by anti-rat MHC class II mAb (MRC OX-6). Autoreactive (Fisher) and alloreactive (Buffalo) T cell lines and isolated CD4+ T cells derived from these lines, which were developed against Fisher rat spleen cells, similarly recognized MHC class II Ag expressed on 1B-6 cells but had no detectable response to 1B-6 MHC class II-negative thyrocytes or MHC class II-positive human thyroid cells. The CD4+ T cell recognition of 1B-6 cells via MHC class II Ag supports our previous data with autologous human thyroid T cell co-cultures and is indicative of an autospecific role for thyrocytes in the development of autoimmune thyroiditis.

Animals↗
PubMed1994

Limited T cell response to donor MHC peptides during allograft rejection. Implications for selective immune therapy in transplantation.

Previously, we have demonstrated that during allograft rejection, MHC molecules of the donor are processed and presented to alloreactive CD4+ T lymphocytes in the form of peptides associated with the MHC class II molecules of the recipient. There is an increasing body of evidence that this indirect pathway of allorecognition may play a major role in allograft rejection. Herein, we have used a series of overlapping MHC peptides progressing along the sequence of the donor MHC molecule in single residue steps. We have mapped all potential MHC Ag determinants to which T cell responses could be generated after s.c. injection of allogeneic splenocytes. We have shown that splenic T cell proliferative responses to the beta 1 domains of donor Ak, Ad, and A(s) mouse MHC class II molecules were directed toward a single immunodominant determinant in each of three donor/recipient combinations. Interestingly, after allogeneic spleen cell transplantation, an additional determinant on donor MHC could be detected in the draining lymph nodes. This result shows that the fine specificity of T cell response to donor transplantation Ags can differ between lymphoid organs. Then, we investigated whether limitation of T cell response to donor MHC peptides applies to the clinical situation of a graft. We have shown that after an allogeneic skin graft, self-restricted alloreactive T cells proliferated to the same determinant on the donor MHC molecule. These results indicate that immune intervention, such as tolerance induction to the dominant T cell determinant on donor MHC molecules, may be developed for the prevention of allograft rejection.

Amino Acid Sequence↗
PubMed1996

The influence of dietary and genetic cues on the ability of rats to discriminate between the urinary odors of MHC-congenic mice.

This study directly compared the role of genetic and dietary factors in the production of individual urinary odors in mice by investigating the ability of male Long-Evans hooded rats to discriminate between urine samples from two strains of mice (C57BL/6-H-2Kb/J and C57BL/6-H-2Kbml/ByJ), which differ at only one locus of the major histocompatibility complex (MHC) and which were maintained on two different diets. Groups of rats were trained in an olfactometer on a go/no-go operant task with water as reinforcement to discriminate between one of the following four pairs of mouse urinary odors: individual mice differing at the MHC and maintained on the same diet (task 1), individual mice differing at the MHC and maintained on different diets (task 2), individual mice of the same MHC type maintained on the same diet (task 3), or individual mice of the same MHC type maintained on different diets (task 4). The urinary odors of mice on different diets (task 2 and 4) were more readily discriminable than those of mice maintained on the same diet (tasks 1 and 3), irrespective of genetic differences at the MHC. It was more difficult to discriminate between urinary odors of mice on the same diet whether they were genetically identical (task 4) or differed at the MHC (task 1). A second experiment revealed that it was no less difficult for rats to discriminate between the urinary odors of mice that differed at three MHC loci than it was for rats to discriminate between two mice that differed at one MHC locus. Thus, the results from Experiment 1 were not caused by the degree of genetic difference at the MHC. Overall, these results provide further evidence that dietary as well as genetic cues contribute to individual odors in rodents, and demonstrate the ability of rats to make very subtle discriminations between odors when trained in an olfactometer.

Animals↗
PubMed1998

MHC class I mosaic mice reveal insights into control of Ly49C inhibitory receptor expression in NK cells.

We have analyzed lymphocyte development in natural MHC class I chimeric mice, generated through a transgenic approach in beta2-microglobulin (beta2m)-/- mice. In these mice, MHC class I+ cells coexist with an equal proportion of MHC class I-deficient cells. These MHC class I mosaic mice had normal numbers of CD8+ T cells, which had a target cell specificity similar to that of wild-type mice. Consequently, the mice did not develop any signs of autoimmunity. They also had normal numbers of NK cells. This allowed an examination of the MHC class I influence on the expression of the Ly49C inhibitory receptor on NK cells. This receptor binds to H-2Kb. It is expressed at low levels on NK cells in wild-type mice of the H-2b haplotype, but at markedly higher levels on NK cells in beta2m-/- mice and other strains of mice lacking expression of H-2Kb. Relatively little is known about how MHC class I molecules affect expression of the Ly49 receptors. Through the analysis of the present MHC class I mosaic mice, we demonstrate that the expression levels of Ly49C on NK cells is a consequence not only of MHC class I expression in the environment, but also of the expression of MHC class I molecules by the NK cells themselves. These findings are discussed in relation to the biological role of the calibration of the Ly49 inhibitory receptor expression in relation to self-MHC class I.

Animals↗
PubMed1997

The MHC reactivity of the T cell repertoire prior to positive and negative selection.

T cell antigen receptors (TCRs) on mature T cells react with peptide antigens presented by self-MHC proteins and also frequently cross-react with foreign MHC proteins. The fundamental question whether MHC reactivity is inherent in the germline TCR sequences or is imposed by thymic selection was addressed here by inducing nonselective maturation of immature thymocytes in the absence of MHC molecules. MHC reactivity in the preselection repertoire is very high, but no higher than in the normal repertoire. Cross-reactivity of clones with multiple MHC molecules occurred to a similar extent in the preselection and MHC-selected repertoires. The results establish the MHC reactivity of the germline TCR repertoire, indicate the minimum fraction of immature thymocytes that must undergo negative selection, and suggest that some TCR-MHC contacts may be conserved.

Animals↗
PubMed2004

Comparative genomic analysis of two avian (quail and chicken) MHC regions.

We mapped two different quail Mhc haplotypes and sequenced one of them (haplotype A) for comparative genomic analysis with a previously sequenced haplotype of the chicken Mhc. The quail haplotype A spans 180 kb of genomic sequence, encoding a total of 41 genes compared with only 19 genes within the 92-kb chicken Mhc. Except for two gene families (B30 and tRNA), both species have the same basic set of gene family members that were previously described in the chicken "minimal essential" Mhc. The two Mhc regions have a similar overall organization but differ markedly in that the quail has an expanded number of duplicated genes with 7 class I, 10 class IIB, 4 NK, 6 lectin, and 8 B-G genes. Comparisons between the quail and chicken Mhc class I and class II gene sequences by phylogenetic analysis showed that they were more closely related within species than between species, suggesting that the quail Mhc genes were duplicated after the separation of these two species from their common ancestor. The proteins encoded by the NK and class I genes are known to interact as ligands and receptors, but unlike in the quail and the chicken, the genes encoding these proteins in mammals are found on different chromosomes. The finding of NK-like genes in the quail Mhc strongly suggests an evolutionary connection between the NK C-type lectin-like superfamily and the Mhc, providing support for future studies on the NK, lectin, class I, and class II interaction in birds.

Animals↗
PubMed1993

RFLP analysis of the MHC class III region defines unique haplotypes for the non-obese diabetic, cataract Shionogi and the non-obese non-diabetic mouse strains.

The non-obese diabetic (NOD) mouse strain which spontaneously develops diabetes is a model for human Type 1 (insulin-dependent) diabetes mellitus. At least one of several genes controlling diabetes in the NOD mouse has been mapped to the MHC. Although previous experiments have implicated the MHC class II genes in the development of the disease, the existence of other MHC linked susceptibility genes has not been ruled out. In order to identify these susceptibility genes we have further characterized the MHC haplotype of the NOD mouse and two non-diabetic sister strains, the non-obese non-diabetic (NON) and cataract Shionogi (CTS). We have examined the mouse MHC class III region for the presence of homologous genes to 17 newly isolated human MHC class III region genes (G1, G2, G4, G6, G7a/valyl-tRNA synthetase, HSP70, G8, G9, G10, G12, G13, G14, G15, G16, G17 and G18). We detect unique hybridizing DNA fragments for 16 of the 17 genes in six inbred mouse strains (NOD, NON, CTS, B10, BALB/c and CBA/J) indicating that this part of the H-2 region is similar to the human MHC class III region. Using a panel of restriction enzymes we have defined RFLPs for 6 (G2, G6, HSP70, G12, G16, G18) of the 16 cross-hybridizing probes. The RFLPs demonstrate that NOD, NON and CTS mouse strains each have a distinct MHC haplotype in the MHC class III region.

Animals↗
PubMed2004

cDNA cloning and genomic structure of the duck (Anas platyrhynchos) MHC class I gene.

In order to provide data for studies on disease resistance, duck MHC class I cDNA (Anpl-MHC I) was cloned from a duck cDNA library and the genome structure was investigated. Anpl-MHC I genes encoded 344-355 amino acids. The genomic organization is composed of eight exons and seven introns. Based on the genetic distance, Anpl-MHC I cDNA from six individuals can be classified into four lineages (from Anpl-UAA to Anpl-UDA). A total of 28 amino acid positions in the peptide-binding domain (PBD) showed high scores by Wu-kabat index analysis. The Anpl-MHC amino acid sequence displayed seven critical HLA-A2amino acids that bind with antigen polypeptides, and have an 83.6-88.5% amino acid homology with each lineage, a 55.2-64.6% amino-acid homology with chicken MHC class I (B-FIV21, B-FIV2, Rfp-Y), and a 40.3-42.8% homology with mammalian MHC class I. Nested PCR detected that Anpl-MHC I can be expressed in the brain, heart, kidney, intestines and bursa. Compared with the human HLA-A2 tertiary structure of the PBD, Anpl-MHC I had an insertion or deletion variation in four domains (A-D). The phlyogenetic tree appears to branch in an order consistent with accepted evolutionary pathways.

Amino Acid Sequence↗
PubMed2006

High levels of diversity characterize mandrill (Mandrillus sphinx) Mhc-DRB sequences.

The major histocompatibility complex (MHC) is highly polymorphic in most primate species studied thus far. The rhesus macaque (Macaca mulatta) has been studied extensively and the Mhc-DRB region demonstrates variability similar to humans. The extent of MHC diversity is relatively unknown for other Old World monkeys (OWM), especially among genera other than Macaca. A molecular survey of the Mhc-DRB region in mandrills (Mandrillus sphinx) revealed extensive variability, suggesting that other OWMs may also possess high levels of Mhc-DRB polymorphism. In the present study, 33 Mhc-DRB loci were identified from only 13 animals. Eleven were wild-born and presumed to be unrelated and two were captive-born twins. Two to seven different sequences were identified for each individual, suggesting that some mandrills may have as many as four Mhc-DRB loci on a single haplotype. From these sequences, representatives of at least six Mhc-DRB loci or lineages were identified. As observed in other primates, some new lineages may have arisen through the process of gene conversion. These findings indicate that mandrills have Mhc-DRB diversity not unlike rhesus macaques and humans.

Alleles↗