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 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-2d 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-2Dd) to conventional CD4- CD8+ CTL mapped by using transfectants expressing Dd, Ld, or Kd, 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.
Shirai
M
M
Third Department of Internal Medicine, Kagawa Medical School, Japan.
Okada
H
H
Nishioka
M
M
Akatsuka
T
T
Wychowski
C
C
Houghten
R
R
Pendleton
C D
CD
Feinstone
S M
SM
Berzofsky
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000939:Epitopes / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006508:Hepatitis Antibodies / Q000097:blood; D006526:Hepatitis C / Q000276:immunology*; D018937:Hepatitis C Antibodies; D006524:Hepatitis, Viral, Animal / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
D000939:Epitopes; D015789:HLA-A2 Antigen; D006508:Hepatitis Antibodies; D018937:Hepatitis C Antibodies; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus