Presence of HLA-C-restricted cytotoxic T-lymphocyte responses in long-termnonprogressors infected with human immunodeficiency virus

Approximately 5% of people with human immunodeficiency virus type 1 (HIV-1) infection remain free of disease for 10 or more years. These long-term non progressors (LTNPs) exhibit lower viral loads and,table CD4(+) lymphocyte c ounts. The immunologic basis for this disease-free condition is not known. Because cytotoxic T lymphocytes (CTLs) constitute a major immune defense me chanism for sustained recovery from viral infections, we analyzed HIV-speci fic CTL responses in three asymptomatic LTNPs. We observed the presence of HIV-1 envelope-specific CTL responses mediated by HLA class I C-restricted CD8(+) cells in these individuals. Using autologous target cells and a pane l of HLA-matching and -mismatching B-cell lines as targets, we determined t hat HLA-Cw7 is the restricting element for the observed CTL activity. Addit ionally, we identified three peptides, one previously not reported, from co nserved regions in the envelope protein as CTL epitopes. We previously repo rted these peptides to be efficient in inducing HIV-specific cellular immun e responses in murine and nonhuman primate models. Our results support the role of the HLA-C locus in generating CTL responses and constitute the firs t report of an HLA-Cw7-restricted HIV-1 envelope-specific CTL response in H IV+ LTNPs, which may be important in the control of HIV replication in vivo .