Identification of novel hepatitis C virus-specific cytotoxic T lymphocyte epitopes by ELISpot assay using peptides with human leukocyte antigen-A*2402-binding motifs.
The human leukocyte antigen (HLA)-A*2402 is common in Asians. The authors attempted to identify epitopes for HLA-A*2402-restricted, hepatitis C virus (HCV)-specific CD8(+) T cells by an enzyme-linked immunospot (ELISpot) assay using peripheral blood CD8(+) T cells from HLA-A*2402-positive hepatitis C patients and synthetic HCV peptides based on HLA-A*2402-binding motifs and the amino acid sequence of type 1b HCV. Ten novel epitopes were identified in five of seven HLA-A*2402-positive patients with acute or short-term chronic HCV infection (<3 years), but in none of four with longer-term chronic infection (>10 years). Only one of the ten epitopes proved to be definitely HLA-A*2402-restricted. Another epitope was identified in one of two HLA-A*2402-negative acute hepatitis C patients. In two of the six patients with positive CD8(+) T cell responses, the targeted epitopes were multiple. The same epitope was targeted in two patients. When patients with unresolved acute HCV infection were treated with alpha interferon, peripheral blood HCV-specific CD8(+) T cells decreased with resolution of the hepatitis. In conclusion, CD8(+) T cell responses to HCV infection are heterogeneous. One definite HLA-A*2402-restricted and ten probably non-HLA-A*2402-restricted epitopes were identified. Patients with short-term HCV infection are suitable for searching for novel HCV epitopes, but peripheral blood HCV-specific CD8(+) T cells decrease markedly after loss of antigenic stimulation.
Hakamada
Taku
T
Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Funatsuki
Kiyomi
K
Research & Development Department, Mitsubishi Kagaku Bio-Clinical Laboratories Inc., 3-30-1 Shimura, Itabashi-ku, Tokyo 174-8555, Japan.
Morita
Hiroki
H
Division of Gastroenterology, Omiya Medical Center, Jichi Medical School, 1-847 Amanuma-cho, Omiya-ku, Saitama 330-8503, Japan.
Ugajin
Takuhiro
T
Division of Gastroenterology, Omiya Medical Center, Jichi Medical School, 1-847 Amanuma-cho, Omiya-ku, Saitama 330-8503, Japan.
Nakamura
Ikuo
I
Division of Gastroenterology, Omiya Medical Center, Jichi Medical School, 1-847 Amanuma-cho, Omiya-ku, Saitama 330-8503, Japan.
Ishiko
Hiroaki
H
Research & Development Department, Mitsubishi Kagaku Bio-Clinical Laboratories Inc., 3-30-1 Shimura, Itabashi-ku, Tokyo 174-8555, Japan.
Matsuzaki
Yasushi
Y
Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Tanaka
Naomi
N
Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Imawari
Michio
M
Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
D001665:Binding Sites; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens / Q000378:metabolism*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D016898:Interferon-alpha; D007371:Interferon-gamma