Unusually High Frequency MHC Class I Alleles in Mauritian Origin Cynomolgus Macaques

Abstract

Acute shortages of Indian origin Rhesus macaques significantly hinder HIV/AIDS research. Cellular immune responses are particularly difficult to study because only a subset of animals possess MHC class I (MHC I) alleles with defined peptide-binding specificities. To expand the pool of nonhuman primates suitable for studies of cellular immunity, we defined 66 MHC I alleles in Cynomolgus macaques (Macaca fascicularis) of Chinese, Vietnamese, and Mauritian origin. Most MHC I alleles were found only in animals from a single geographic origin, suggesting that Cynomolgus macaques from different origins are not interchangeable in studies of cellular immunity. Animals from Mauritius may be particularly valuable because >50% of these Cynomolgus macaques share the MHC class I allele combination Mafa-B*430101, Mafa-B*440101, and Mafa-B*460101. The increased MHC I allele sharing of Mauritian origin Cynomolgus macaques may dramatically reduce the overall number of animals needed to study cellular immune responses in nonhuman primates while simultaneously reducing the confounding effects of genetic heterogeneity in HIV/AIDS research.

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

“…They differ from Mafa-B*390101 (GenBank accession no. AY969136 31 ) by only one or two nucleotides. The splice variants are nonfunctional as they contain a frame shift mutation at the beginning of exon 3 due to a deletion of 74 bp.…”

Simian Immunodeficiency Virus SIVmac239 Infection of Major Histocompatibility Complex-Identical Cynomolgus Macaques from Mauritius

“…Blood samples from feral MCM were purchased directly for genetic analyses (Charles River BRF, Houston, TX). Our initial microsatellite analysis focused on five MCM that were examined previously in an MHC class I allele discovery study (20). Subsequently, blood from another 112 feral MCM was obtained in two independent shipments from Charles River BRF for MHC class I genotyping.…”

“…Transcribed MHC class I alleles were genotyped by reference strand conformation analysis (RSCA) of cDNA heteroduplexes from peripheral blood mononuclear cells or whole blood essentially as described previously (20) with the following modification. A 304-bp amplicon was amplified by PCR from cDNA in order to scan additional polymorphic sites in the highly variable peptide binding domains encoded by exons 2 and 3 using the 5Ј phosphate (Phos)-modified primer 5ЈP-Refstrand (5Ј-[Phos]GCTACGTGGACGAC ACGC-3Ј) and Short3ЈRSCA (5Ј-TTCAGGGCGATGTAATCC-3Ј).…”

“…In the contemporary Finnish human population, which descends from a limited number of ancestors within approximately the same number of generations as MCM, entire shared MHC haplotypes are common (17). Thus, we hypothesized that the unusual natural history of MCM might portend the presence of high-frequency MHC haplotypes (20). We discovered that six high-frequency haplotypes encompassing both the MHC class I and class II loci account for almost all MHC diversity in MCM.…”

Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: Influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV89.6P infection

“…As the entire repertoire of MHC alleles can now be predicted for essentially all Mauritian cynomolgus macaques [35][36][37], we also determined the MHC genotypes of the study animals. These investigations revealed a new association of Mauritian MHC haplotype and susceptibility/resistance to SHIV 89.6P infection.…”