Transcriptionally abundant major histocompatibility complex class I alleles are fundamental to nonhuman primate simian immunodeficiency virus-specific CD8+ T cell responses

Melisa L. Budde, Jennifer J. Lhost, Benjamin J. Burwitz, Ericka A. Becker, Charles M. Burns, Shelby L. O'Connor, Julie A. Karl, Roger W. Wiseman, Benjamin N. Bimber, Guang Lan Zhang, William Hildebrand, Vladimir Brusic, David H. O'Connor

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Simian immunodeficiency virus (SIV)-infected macaques are the preferred animal model for human immunodeficiency virus (HIV) vaccines that elicit CD8+ T cell responses. Unlike humans, whose CD8+ T cell responses are restricted by a maximum of six HLA class I alleles, macaques express up to 20 distinct major histocompatibility complex class I (MHC-I) sequences. Interestingly, only a subset of macaque MHC-I sequences are transcriptionally abundant in peripheral blood lymphocytes. We hypothesized that highly transcribed MHC-I sequences are principally responsible for restricting SIV-specific CD8+ T cell responses. To examine this hypothesis, we measured SIV-specific CD8+ T cell responses in MHC-I homozygous Mauritian cynomolgus macaques. Each of eight CD8+ T cell responses defined by full-proteome gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay were restricted by four of the five transcripts that are transcriptionally abundant (>1% of total MHC-I transcripts in peripheral blood lymphocytes). The five transcriptionally rare transcripts shared by these animals did not restrict any detectable CD8+ T cell responses. Further, seven CD8+ T cell responses were defined by identifying peptide binding motifs of the three most frequent MHC-I transcripts on the M3 haplotype. Combined, these results suggest that transcriptionally abundant MHC-I transcripts are principally responsible for restricting SIV-specific CD8 + T cell responses. Thus, only a subset of the thousands of known MHC-I alleles in macaques should be prioritized for CD8+ T cell epitope characterization.

Original languageEnglish
Pages (from-to)3250-3261
Number of pages12
JournalJournal of Virology
Volume85
Issue number7
DOIs
Publication statusPublished - Apr 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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