Major histcompatibility complex (MHC) class I and class II molecules bind and present immunogenic peptides to CD8+ and CD4+ T cells, respectively. These molecules are critically important for transplant tolerance and infectious disease research. The genes encoding MHC class I and class II molecules are among the most polymorphic in the genome. As of April 2015, over 10,000 MHC allelic variants have been described in humans.
Nonhuman primates - particularly macaque monkeys - are essential animal models for transplantation and infectious disease research. MHC genetics of macaques differ from human in several critical ways:
- Each human MHC class I haplotype encodes three classical MHC alleles: HLA-A, HLA-B, and HLA-C. Macaque haplotypes encode a much greater, variable number of alleles. The single macaque haplotype sequenced in its entirety contains 64 MHC class I genes
- All three human MHC class I genes are co-dominantly expressed. Macaque MHC class I genes are not. Only a small subset of the genes (approximately 3-5 per haplotype) are present in greater than 1% of the transcript pool in blood. Many MHC class I genes are not expressed at all or are expressed at vanishingly low levels
- The total number of macaque MHC sequences is likely larger than the number of human MHC sequences, given the evolutionary distance of the macaques. Some MHC alleles are shared between multiple macaque species, but many are private to single species and, in some cases, specific geographic subpopulations within a species
Consequently, determining MHC genotypes of macaques requires different approaches than are used in humans. There is also a pressing need to define additional MHC variants to create comprehensive databases that can be used for accurate, unambiguous genotyping. The National Institute of Allergy and Infectious Diseases responded to these needs by funding two contracts to the University of Wisconsin-Madison and the Biomedical Primate Research Centre. The first was funded in 2004 and the second was funded in 2011. This site is a clearinghouse for information generated by this contract, including protocols for genotyping and allele discovery, information about MHC alleles in different macaque populations, materials from training workshops, and an intranet for collaboration between contract staff and NIH-authorized users. Use the menu above to browse the site.
In addition to the content available here, there are two other websites that may be useful for researchers interested in nonhuman primate MHC genetics:
- IPD-MHC Non-Human Primates (NHP) - a manually curated repository of NHP allelic variants. The 2011 NIAID contract also provides partial support for management of this repository. It is a much more accurate representation of MHC alleles than NCBI Genbank due to its strict adherence to nomenclature standards and careful curation.
- Wisconsin National Primate Research Center Genetics Services - a nonhuman primate MHC genotyping service that makes genotyping technologies developed under this contract available to the scientific community on a fee-for-service basis