Immunodominant HIV-Specific CD8 T-Cell Responses Are Common

Previous studies have suggested that polyfunctional mucosal CD8 T-cell responses may be a correlate of protection in HIV controllers. Mucosal T-cell breadth and/or specificity may also contribute to defining protective responses. In this study, rectal CD8 T-cell responses to HIV Gag, Env, and Nef were mapped at the peptide level in four subject groups: elite controllers (n 16; viral load [VL], <75 copies/ml), viremic controllers (n 14; VL, 75 to 2,000 copies/ml), noncontrollers (n 14; VL,>10,000 copies/ml), and antiret-roviral-drug-treated subjects (n 8; VL, <75 copies/ml). In all subject groups, immunodominant CD8 T-cell responses were generally shared by blood and mucosa, although there were exceptions. In HIV controllers, responses to HLA-B27- and HLA-B57-restricted epitopes were common to both tissues, and their magnitude (in spot-forming cells [SFC] per million) was significantly greater than those of responses restricted by other alleles. Furthermore, peptides recognized by T cells in both blood and rectal mucosa, termed “concordant,” elicited higher median numbers of SFC than discordant responses. In magnitude as well as breadth, HIV Gag-specific responses, particularly those targeting p24 and p7, dominated in controllers. Responses in noncontrollers were more evenly distributed among epitopes in Gag, Env, and Nef. Viremic controllers showe