AN EPITOPE IN HEPATITIS-C VIRUS CORE REGION RECOGNIZED BY CYTOTOXIC T-CELLS IN MICE AND HUMANS

Several cytotoxic T-lymphocyte (CTL) epitopes have been defined in hep atitis C virus (HCV) proteins. CTL may play an important role in the c ontrol of infection by HCV. Here, we identify a highly conserved antig enic site in the HCV core recognized by both murine and human CTL. Spl een cells from mice immunized with a recombinant vaccinia virus expres sing the HCV core gene were restimulated in vitro with 11 peptides fro m the core protein. CTL from H-2(d) mice responded to a single 16-resi due synthetic peptide (HCV 129-144). This conserved epitope was presen ted by a murine class I major histocompatibility molecule (H-2D(d)) to conventional CD4(-) CD8(+) CTL mapped by using transfectants expressi ng D-d, L(d), or K-d, but was not seen by CTL restricted by H-2(b). Th e murine epitope was mapped to the decapeptide LMGYIPLVGA. The same 16 -residue peptide was recognized by CTL from two HCV-seropositive patie nts but not by CTL from any seronegative donors. CTL from two HLA-A2-p ositive patients with acute and chronic hepatitides C recognized a 9-r esidue fragment (DLMGYIPLV) of the peptide presented by BLA-A2 and con taining an HLA-A2-binding motif, extending only 1 residue beyond the m urine epitope. Therefore, this conserved peptide, seen with murine CTL and human CTL with a very prevalent HLA class I molecule, may be a va luable component of an HCV vaccine against a broad range of HCV isolat es. This study demonstrates that the screening: for CTL epitopes in mi ce prior to human study may be useful.