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

Benjamin J. Burwitz, Chad J. Pendley, Justin M. Greene, Ann M. Detmer, Jennifer J. Lhost, Julie A. Karl, Shari M. Piaskowski, Richard A. Rudersdorf, Lyle T. Wallace, Benjamin N. Bimber, John T. Loffredo, Daryl G. Cox, Wilfried Bardet, William Hildebrand, Roger W. Wiseman, Shelby L. O'Connor, David H. O'Connor

Research output: Contribution to journalArticle

53 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6011-6019
Number of pages9
JournalJournal of virology
Volume83
Issue number12
DOIs
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Burwitz, B. J., Pendley, C. J., Greene, J. M., Detmer, A. M., Lhost, J. J., Karl, J. A., Piaskowski, S. M., Rudersdorf, R. A., Wallace, L. T., Bimber, B. N., Loffredo, J. T., Cox, D. G., Bardet, W., Hildebrand, W., Wiseman, R. W., O'Connor, S. L., & O'Connor, D. H. (2009). Mauritian cynomolgus macaques share two exceptionally common major histocompatibility complex class I alleles that restrict simian immunodeficiency virus-specific CD8+ T cells. Journal of virology, 83(12), 6011-6019. https://doi.org/10.1128/JVI.00199-09