Identification of A2-restricted hepatitis C virus-specific cytotoxic T lymphocyte epitopes from conserved regions of the viral genome.
We have focused on conserved regions of the hepatitis C Virus (HCV) genome to identify viral peptides that contain HLA class I binding motifs and bind with high affinity to the corresponding purified HLA molecules. Accordingly, we have identified 31 candidate epitopes in the HCV that have the potential to be recognized by either HLA-A1, A2.1-, A3, A11- or A24-restricted cytotoxic T lymphocytes (CTL). Twelve conserved peptides that bind HLA-A2.1 with high or intermediate affinity were tested for immunogenicity in vitro in human primary CTL cultures and in vivo by direct immunization of HLA-A2.1/Kb transgenic mice. Six HLA-A2.1-restricted CTL epitopes were immunogenic in both systems. At least three of these peptide epitopes were endogenously processed and presented for CTL recognition. Overall, these data illustrate the value of this approach for the development of virus-specific, peptide-based vaccines.
Wentworth
P A
PA
Cytel Corporation, San Diego, CA 92121, USA.
Sette
A
A
Celis
E
E
Sidney
J
J
Southwood
S
S
Crimi
C
C
Stitely
S
S
Keogh
E
E
Wong
N C
NC
Livingston
B
B
Alazard
D
D
Vitiello
A
A
Grey
H M
HM
Chisari
F V
FV
Chesnut
R W
RW
Fikes
J
J
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology*; D016174:Hepacivirus / Q000145:classification / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection / Q000276:immunology
D000939:Epitopes; D015789:HLA-A2 Antigen