title: Mauritian cynomolgus macaques share two exceptionally common major histocompatibility complex class I alleles that restrict simian immunodeficiency virus-specific CD8+ T cells.
abstract: Vaccines that elicit CD8(+) T-cell responses are routinely tested for immunogenicity in nonhuman primates before advancement to clinical trials. Unfortunately, the magnitude and specificity of vaccine-elicited T-cell responses are variable in currently utilized nonhuman primate populations, owing to heterogeneity in major histocompatibility (MHC) class I genetics. We recently showed that Mauritian cynomolgus macaques (MCM) have unusually simple MHC genetics, with three common haplotypes encoding a shared pair of MHC class IA alleles, Mafa-A*25 and Mafa-A*29. Based on haplotype frequency, we hypothesized that CD8(+) T-cell responses restricted by these MHC class I alleles would be detected in nearly all MCM. We examine here the frequency and functionality of these two alleles, showing that 88% of MCM express Mafa-A*25 and Mafa-A*29 and that animals carrying these alleles mount three newly defined simian immunodeficiency virus-specific CD8(+) T-cell responses. The epitopes recognized by each of these responses accumulated substitutions consistent with immunologic escape, suggesting these responses exert antiviral selective pressure. The demonstration that Mafa-A*25 and Mafa-A*29 restrict CD8(+) T-cell responses that are shared among nearly all MCM indicates that these animals are an advantageous nonhuman primate model for comparing the immunogenicity of vaccines that elicit CD8(+) T-cell responses.
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Burwitz
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Pendley
authors.forename: Justin M
authors.initials: JM
authors.lastname: Greene
authors.forename: Ann M
authors.initials: AM
authors.lastname: Detmer
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Lhost
authors.forename: Julie A
authors.initials: JA
authors.lastname: Karl
authors.forename: Shari M
authors.initials: SM
authors.lastname: Piaskowski
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudersdorf
authors.forename: Lyle T
authors.initials: LT
authors.lastname: Wallace
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Bimber
authors.forename: John T
authors.initials: JT
authors.lastname: Loffredo
authors.forename: Daryl G
authors.initials: DG
authors.lastname: Cox
authors.forename: Wilfried
authors.initials: W
authors.lastname: Bardet
authors.forename: William
authors.initials: W
authors.lastname: Hildebrand
authors.forename: Roger W
authors.initials: RW
authors.lastname: Wiseman
authors.forename: Shelby L
authors.initials: SL
authors.lastname: O'Connor
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor