We studied the induction of T cell responses against hepatitis C virus (HCV)-related cytotoxic T cell (CTL) epitopes in lymphocytes from human leukocyte antigen (HLA)-A2-positive, HCV-naive individuals. Peptide and lipopeptides corresponding to the epitope at amino acids (aa) 1073-1081 induced equivalent numbers of tetramer-positive CD8+ T cells and detectable interferon-gamma and granzyme B spot-forming cells (sfcs). Epitope aa 35-44 induction of CTLs was not achieved, despite detectable tetramer-positive CD8+ T cells. IFN-gamma sfcs could only be induced with lipopeptide aa 20-44 but not by conventional antigens, which indicates that lipopeptides may alter T cell functions, depending on the epitope.