Mauritian cynomolgus macaques share two exceptionally common major histocompatibility complex class I alleles that restrict simian immunodeficiency virus-specific CD8+ T cells

J Virol. 2009 Jun;83(12):6011-9. doi: 10.1128/JVI.00199-09. Epub 2009 Apr 1.

Abstract

Vaccines that elicit CD8(+) T-cell responses are routinely tested for immunogenicity in nonhuman primates before advancement to clinical trials. Unfortunately, the magnitude and specificity of vaccine-elicited T-cell responses are variable in currently utilized nonhuman primate populations, owing to heterogeneity in major histocompatibility (MHC) class I genetics. We recently showed that Mauritian cynomolgus macaques (MCM) have unusually simple MHC genetics, with three common haplotypes encoding a shared pair of MHC class IA alleles, Mafa-A*25 and Mafa-A*29. Based on haplotype frequency, we hypothesized that CD8(+) T-cell responses restricted by these MHC class I alleles would be detected in nearly all MCM. We examine here the frequency and functionality of these two alleles, showing that 88% of MCM express Mafa-A*25 and Mafa-A*29 and that animals carrying these alleles mount three newly defined simian immunodeficiency virus-specific CD8(+) T-cell responses. The epitopes recognized by each of these responses accumulated substitutions consistent with immunologic escape, suggesting these responses exert antiviral selective pressure. The demonstration that Mafa-A*25 and Mafa-A*29 restrict CD8(+) T-cell responses that are shared among nearly all MCM indicates that these animals are an advantageous nonhuman primate model for comparing the immunogenicity of vaccines that elicit CD8(+) T-cell responses.

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Animals
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Epitopes, T-Lymphocyte / immunology
  • Gene Frequency
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Macaca fascicularis / genetics*
  • Macaca fascicularis / immunology
  • Microsatellite Repeats
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I