title: 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.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, WI 53711, USA. njmaness@wisc.edu
authors.forename: Nicholas James
authors.initials: NJ
authors.lastname: Maness
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Walsh
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudersdorf
authors.forename: Priscilla A
authors.initials: PA
authors.lastname: Erickson
authors.forename: Shari M
authors.initials: SM
authors.lastname: Piaskowski
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002681:China; D005805:Genes, MHC Class I / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D007194:India; D008253:Macaca mulatta / Q000276:immunology*; D008969:Molecular Sequence Data; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes