Abstract
Successful human immunodeficiency virus (HIV) vaccines will need to induce effective T-cell immunity. We studied immunodominant simian immunodeficiency virus (SIV) Gag-specific T-cell responses and their restricting major histocompatibility complex (MHC) class I alleles in pigtail macaques (
Macaca nemestrina
), an increasingly common primate model for the study of HIV infection of humans. CD8
+
T-cell responses to an SIV epitope, Gag
164
-
172
KP9, were present in at least 15 of 36 outbred pigtail macaques. The immunodominant KP9-specific response accounted for the majority (mean, 63%) of the SIV Gag response. Sequencing from six macaques identified 7 new
Mane-A
and 13 new
Mane-B
MHC class I alleles. One new allele,
Mane-A*10
, was common to four macaques that responded to the KP9 epitope. We adapted reference strand-mediated conformational analysis (RSCA) to MHC class I genotype
M. nemestrina. Mane-A*10
was detected in macaques presenting KP9 studied by RSCA but was absent from non-KP9-presenting macaques. Expressed on class I-deficient cells, Mane-A*10, but not other pigtail macaque MHC class I molecules, efficiently presented KP9 to responder T cells, confirming that
Mane-A*10
restricts the KP9 epitope. Importantly, naïve pigtail macaques infected with SIV
mac251
that respond to KP9 had significantly reduced plasma SIV viral levels (log
10
0.87 copies/ml;
P
= 0.025) compared to those of macaques not responding to KP9. The identification of this common
M. nemestrina
MHC class I allele restricting a functionally important immunodominant SIV Gag epitope establishes a basis for studying CD8
+
T-cell responses against AIDS in an important, widely available nonhuman primate species.
