HLA-B27- and -B57-positive HIV-infected humans have long been associated with control of HIV replication, implying that CD8(+) T cell responses contribute to control of viral replication. In a similar fashion, 50% of Mamu-B*08-positive Indian rhesus macaques control SIVmac239 replication and become elite controllers with chronic-phase
viremia <1000
viral RNA copies/ml. Interestingly, Mamu-B*08-restricted SIV-derived
epitopes appeared to match the
peptide binding profile for
HLA-B*2705 in humans. We therefore defined a detailed
peptide-binding motif for Mamu-B*08 and investigated binding similarities between the macaque and human
MHC class I molecules. Analysis of a panel of approximately 900
peptides revealed that despite substantial sequence differences between Mamu-B*08 and
HLA-B*2705, the
peptide-binding repertoires of these two
MHC class I molecules share a remarkable degree of overlap. Detailed knowledge of the Mamu-B*08
peptide-binding motif enabled us to identify six additional novel Mamu-B*08-restricted SIV-specific CD8(+) T cell immune responses directed against
epitopes in Gag, Vpr, and Env. All 13 Mamu-B*08-restricted
epitopes contain an R at the position 2 primary anchor and 10 also possess either R or K at the N terminus. Such dibasic
peptides are less prone to cellular degradation. This work highlights the relevance of the Mamu-B*08-positive SIV-infected Indian rhesus macaque as a model to examine elite control of immunodeficiency virus replication. The remarkable similarity of the
peptide-binding motifs and repertoires for Mamu-B*08 and
HLA-B*2705 suggests that the nature of the
peptide bound by the
MHC class I molecule may play an important role in control of immunodeficiency virus replication.