Chinese origin rhesus macaque major histocompatibility complex class i molecules promiscuously present epitopes from SIV associated with molecules of Indian origin; Implications for immunodominance and viral escape

Nicholas James Maness, Andrew D. Walsh, Richard A. Rudersdorf, Priscilla A. Erickson, Shari M. Piaskowski, Nancy A. Wilson, David I. Watkins

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The presentation of identical peptides by different major histocompatibility complex class I (MHC-I) molecules, termed promiscuity, is a controversial feature of T cell-mediated immunity to pathogens. The astounding diversity of MHC-I molecules in human populations, presumably to enable binding of equally diverse peptides, implies promiscuity would be a rare phenomenon. However, if it occurs, it would have important implications for immunity. We screened 77 animals for responses to peptides known to bind MHC-I molecules that were not expressed by these animals. Some cases of supposed promiscuity were determined to be the result of either non-identical optimal peptides or were simply not mapped to the correct MHC-I molecule in previous studies. Cases of promiscuity, however, were associated with alterations of immunodominance hierarchies, either in terms of the repertoire of peptides presented by the different MHC-I molecules or in the magnitude of the responses directed against the epitopes themselves. Specifically, we found that the Mamu-B*017:01- restricted peptides Vif HW8 and cRW9 were also presented by Mamu-A2*05:26 and targeted by an animal expressing that allele. We also found that the normally subdominant Mamu-A1*001:01 presented peptide Gag QI9 was also presented by Mamu-B*056:01. Both A2*05:26 and B*056:01 are molecules typically or exclusively expressed by animals of Chinese origin. These data clearly demonstrate that MHC-I epitope promiscuity, though rare, might have important implications for immunodominance and for the transmission of escape mutations, depending on the relative frequencies of the given alleles in a population.

Original languageEnglish (US)
Pages (from-to)587-597
Number of pages11
JournalImmunogenetics
Volume63
Issue number9
DOIs
StatePublished - Sep 2011

Keywords

  • CD8+ T lymphocyte
  • Epitope promiscuity
  • Macaca mulatta
  • Major histocompatibility complex
  • Simian immunodeficiency virus

ASJC Scopus subject areas

  • Immunology
  • Genetics

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