Transcriptionally Abundant Major Histocompatibility Complex Class I Alleles Are Fundamental to Nonhuman Primate Simian Immunodeficiency Virus-Specific CD8+T Cell Responses
- 1 April 2011
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 85 (7), 3250-3261
- https://doi.org/10.1128/jvi.02355-10
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.Keywords
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