Mauritian cynomolgus macaques share two exceptionally common major histocompatibility complex class I alleles that restrict simian immunodeficiency virus-specific CD8+ T cells.
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.
Burwitz
Benjamin J
BJ
Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Pendley
Chad J
CJ
Greene
Justin M
JM
Detmer
Ann M
AM
Lhost
Jennifer J
JJ
Karl
Julie A
JA
Piaskowski
Shari M
SM
Rudersdorf
Richard A
RA
Wallace
Lyle T
LT
Bimber
Benjamin N
BN
Loffredo
John T
JT
Cox
Daryl G
DG
Bardet
Wilfried
W
Hildebrand
William
W
Wiseman
Roger W
RW
O'Connor
Shelby L
SL
O'Connor
David H
DH