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. Gag206–216 and Gag241–249 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, Nef9–19, Nef89–97, and Nef193–203, associated with 90-120-Ia. Nef9–19 and Nef193–203 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.