An epitope in hepatitis C virus core region recognized by cytotoxic T cells in mice and humans Article

Shirai, M, Okada, H, Nishioka, M et al. (1994). An epitope in hepatitis C virus core region recognized by cytotoxic T cells in mice and humans . 68(5), 3334-3342. 10.1128/jvi.68.5.3334-3342.1994

cited authors

  • Shirai, M; Okada, H; Nishioka, M; Akatsuka, T; Wychowski, C; Houghten, R; David Pendleton, C; Feinstone, SM; Berzofsky, JA

abstract

  • Several cytotoxic T-lymphocyte (CTL) epitopes have been defined in hepatitis C virus (HCV) proteins. CTL may play an important role in the control of infection by HCV. Here, we identify a highly conserved antigenic site in the HCV core recognized by both murine and human CTL. Spleen cells from mice immunized with a recombinant vaccinia virus expressing the HCV core gene were restimulated in vitro with 11 peptides from the core protein. CTL from H-2(d) mice responded to a single 16-residue synthetic peptide (HCV 129- 144). This conserved epitope was presented by a murine class I major histocompatibility molecule (H-2D(d)) to conventional CD4- CD8+ CTL mapped by using transfectants expressing D(d), L(d), or K(d), but was not seen by CTL restricted by H-2b. The murine epitope was mapped to the decapeptide LMGYIPLVGA. The same 16-residue peptide was recognized by CTL from two HCV- seropositive patients but not by CTL from any seronegative donors. CTL from two HLA-A2-positive patients with acute and chronic hepatitides C recognized a 9-residue fragment (DLMGYIPLV) of the peptide presented by HLA-A2 and containing an HLA-A2-binding motif, extending only 1 residue beyond the murine epitope. Therefore, this conserved peptide, seen with murine CTL and human CTL with a very prevalent HLA class I molecule, may be a valuable component of an HCV vaccine against a broad range of HCV isolates. This study demonstrates that the screening for CTL epitopes in mice prior to human study may be useful.

publication date

  • January 1, 1994

Digital Object Identifier (DOI)

start page

  • 3334

end page

  • 3342

volume

  • 68

issue

  • 5