Transcriptionally abundant major histocompatibility complex class I alleles are fundamental to nonhuman primate simian immunodeficiency virus-specific CD8+ T cell responses.
Journal Article (Journal Article)
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.
- Budde, ML; Lhost, JJ; Burwitz, BJ; Becker, EA; Burns, CM; O'Connor, SL; Karl, JA; Wiseman, RW; Bimber, BN; Zhang, GL; Hildebrand, W; Brusic, V; O'Connor, DH
- April 2011
Volume / Issue
- 85 / 7
Start / End Page
- 3250 - 3261
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States