Abstract
The role of CD4
+
T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication is not well understood. Even though strong HIV- and SIV-specific CD4
+
T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4
+
T-cell response. Here, we describe five macaque MHC-II alleles (
Mamu
-
DRB
*
w606
, -
DRB
*
w2104
, -
DRB1
*
0306
, -
DRB1
*
1003
, and -
DPB1
*
06
) that restricted six SIV-specific CD4
+
T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-II alleles,
Mamu
-
DRB1
*
1003
and -
DRB1
*
0306
, were enriched in this EC group (
P
values of 0.02 and 0.05, respectively). Additionally,
Mamu
-
B
*
17
-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than
Mamu
-
B
*
17
-positive animals that did not express
Mamu
-
DRB1
*
1003
and -
DRB1
*
0306
(
P
value of <0.0001). The study of MHC-II alleles in macaques that control viral replication could improve our understanding of the role of CD4
+
T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design.
