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Characterization of major histocompatibility complex-related molecule 1 sequence variants in non-human primates.

ABSTRACT: The major histocompatibility complex (MHC) class I-related molecule, MR1, presents vitamin B metabolites from bacteria and yeast to mucosal-associated invariant T (MAIT) cells. Despite the evolutionary conservation of MR1, we do not know whether different allele variants of MR1 exist within the nonhuman primate (NHP) populations that are commonly used for biomedical research. In this study, we identified 21 distinct MR1 nucleotide sequences representing 32 different alleles across five different NHP populations. The majority of the alleles conferring amino acid changes (allele variants) were found in or near the alpha-1 domain of the mature MR1 protein. We expressed four of the most commonly observed MR1 allele variants in 293T cells, and we found that each variant could present bacterial metabolites on the cell surface. We successfully induced cytokine production in macaque MAIT cells stimulated with 293T cells expressing the four most common MR1 allele variants, demonstrating the usefulness of these cell lines to study MAIT cell activity. Our data suggests that MR1 is not monomorphic, but that there are multiple MR1 alleles in NHPs. The materials we describe here will be valuable for characterizing differences in MR1 antigen presentation and MAIT cell function in NHPs.

SUBMITTER: Ellis-Connell AL

PROVIDER: S-EPMC6446917 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Characterization of major histocompatibility complex-related molecule 1 sequence variants in non-human primates.

Ellis-Connell Amy L AL Kannal Nadean M NM Balgeman Alexis J AJ O'Connor Shelby L SL

Immunogenetics 20181023 2

The major histocompatibility complex (MHC) class I-related molecule, MR1, presents vitamin B metabolites from bacteria and yeast to mucosal-associated invariant T (MAIT) cells. Despite the evolutionary conservation of MR1, we do not know whether different allele variants of MR1 exist within the nonhuman primate (NHP) populations that are commonly used for biomedical research. In this study, we identified 21 distinct MR1 nucleotide sequences representing 32 different alleles across five different ...[more]

PMID: 30353260

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Project description:BACKGROUND: The ovine Major Histocompatibility Complex (MHC) harbors clusters of genes involved in overall resistance/susceptibility of an animal to infectious pathogens. However, only a limited number of ovine MHC genes have been identified and no adequate sequence information is available, as compared to those of swine and bovine. We previously constructed a BAC clone-based physical map that covers entire class I, class II and class III region of ovine MHC. Here we describe the assembling of a complete DNA sequence map for the ovine MHC by shotgun sequencing of 26 overlapping BAC clones. RESULTS: DNA shotgun sequencing generated approximately 8-fold genome equivalent data that were successfully assembled into a finished sequence map of the ovine MHC. The sequence map spans approximately 2,434,000 nucleotides in length, covering almost all of the MHC loci currently known in the sheep and cattle. Gene annotation resulted in the identification of 177 protein-coding genes/ORFs, among which 145 were not previously reported in the sheep, and 10 were ovine species specific, absent in cattle or other mammals. A comparative sequence analyses among human, sheep and cattle revealed a high conservation in the MHC structure and loci order except for the class II, which were divided into IIa and IIb subregions in the sheep and cattle, separated by a large piece of non-MHC autosome of approximately 18.5 Mb. In addition, a total of 18 non-protein-coding microRNAs were predicted in the ovine MHC region for the first time. CONCLUSION: An ovine MHC DNA sequence map was successfully assembled by shotgun sequencing of 26 overlapping BAC clone. This makes the sheep the second ruminant species for which the complete MHC sequence information is available for evolution and functional studies, following that of the bovine. The results of the comparative analysis support a hypothesis that an inversion of the ancestral chromosome containing the MHC has shaped the MHC structures of ruminants, as we currently observed in the sheep and cattle. Identification of relative large numbers of microRNAs in the ovine MHC region helps to provide evidence that microRNAs are actively involved in the regulation of MHC gene expression and function.

Dataset Information

Characterization of major histocompatibility complex-related molecule 1 sequence variants in non-human primates.

Publications

Characterization of major histocompatibility complex-related molecule 1 sequence variants in non-human primates.

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