A new epitope peptide derived from hepatitis C virus 1b possessing the capacity to induce cytotoxic T-lymphocytes in HCV1b-infected patients with HLA-A11, -A31, and -A33.
BACKGROUND
Hepatitis C virus (HCV) frequently causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma after long-term persistent infection. Among various genotypes of HCV, HCV1b is resistant to standard interferon therapy, and thus the development of new treatment modality is needed.


RESULTS
To provide a scientific basis for specific immunotherapy for HCV1b, we investigated HCV1b-derived epitope peptides recognized by human leukocyte antigen (HLA)-A11, -A31, or -A33-restricted cytotoxic T-lymphocytes (CTLs), and report here three novel vaccine candidate peptides selected by both antibody screening and CTL-inducing capacity from among 46 peptides of conserved regions of HCV1b sequences with binding motifs to HLA-A11, -A31, and -A33. Significant levels of IgG reactive to each of the three peptides were detected in the plasma of more than 50% of the HCV1b(+) patients. One peptide at positions 30-39 of the core protein induced peptide-specific CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A11(+), -A31(+), and -A33(+) patients. The other two peptides at positions 35-43 of the core protein and at positions 918-926 of the non-structural protein 2 also induced peptide-specific CTLs from the PBMCs of HLA-A11(+) and -A33(+) patients.


CONCLUSIONS
Therefore, the peptide at positions 30-39 of the core protein could be an appropriate target molecule of specific immunotherapy for all HLA-A11(+), -A31(+), and -A33(+) patients with HCV1b-related diseases.
Matsueda
Satoko
S
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, 830-0011, Japan.
Yamada
Akira
A
Takao
Yukari
Y
Tamura
Mayumi
M
Komatsu
Nobukazu
N
Yutani
Shigeru
S
Ide
Tatsuya
T
Sata
Michio
M
Itoh
Kyogo
K
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D015234:HLA-A Antigens / Q000737:chemistry / Q000276:immunology*; D059870:HLA-A11 Antigen; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000097:blood / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D000939:Epitopes; D015234:HLA-A Antigens; C082945:HLA-A*33 antigen; D059870:HLA-A11 Antigen; C069527:HLA-A31 antigen; D007074:Immunoglobulin G; D010455:Peptides