Identification of SIV Nef CD8(+) T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model.

Abstract Virus-specific CD8 + T-cell responses are crucial for the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. Multiple studies on HIV-infected individuals and SIV-infected macaques have indicated association of several major histocompatibility complex class I (MHC-I) genotypes with lower viral loads and delayed AIDS progression. Understanding of the viral control mechanism associated with these MHC-I genotypes would contribute to the development of intervention strategy for HIV control. We have previously reported a rhesus MHC-I haplotype, 90-120-Ia , associated with lower viral loads after SIVmac239 infection. Gag 206–216 and Gag 241–249 epitope-specific CD8 + T-cell responses have been shown to play a central role in the reduction of viral loads, whereas the effect of Nef-specific CD8 + T-cell responses induced in all the 90-120-Ia + macaques on SIV replication remains unknown. Here, we identified three CD8 + T-cell epitopes, Nef 9–19 , Nef 89–97 , and Nef 193–203 , associated with 90-120-Ia . Nef 9–19 and Nef 193–203 epitope-specific CD8 + T-cell responses frequently selected for mutations resulting in viral escape from recognition by these CD8 + T cells, indicating that these CD8 + T cells exert strong suppressive pressure on SIV replication. Results would be useful for elucidation of the viral control mechanism associated with 90-120-Ia .