PMID- 15166436 OWN - NLM STAT- MEDLINE DCOM- 20040624 LR - 20200303 IS - 0022-1317 (Print) IS - 0022-1317 (Linking) VI - 85 IP - Pt 6 DP - 2004 Jun TI - Identification of novel hepatitis C virus-specific cytotoxic T lymphocyte epitopes by ELISpot assay using peptides with human leukocyte antigen-A*2402-binding motifs. PG - 1521-1531 LID - 10.1099/vir.0.79801-0 [doi] AB - 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. FAU - Hakamada, Taku AU - Hakamada T AD - Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan. FAU - Funatsuki, Kiyomi AU - Funatsuki K AD - Research & Development Department, Mitsubishi Kagaku Bio-Clinical Laboratories Inc., 3-30-1 Shimura, Itabashi-ku, Tokyo 174-8555, Japan. FAU - Morita, Hiroki AU - Morita H AD - Division of Gastroenterology, Omiya Medical Center, Jichi Medical School, 1-847 Amanuma-cho, Omiya-ku, Saitama 330-8503, Japan. FAU - Ugajin, Takuhiro AU - Ugajin T AD - Division of Gastroenterology, Omiya Medical Center, Jichi Medical School, 1-847 Amanuma-cho, Omiya-ku, Saitama 330-8503, Japan. FAU - Nakamura, Ikuo AU - Nakamura I AD - Division of Gastroenterology, Omiya Medical Center, Jichi Medical School, 1-847 Amanuma-cho, Omiya-ku, Saitama 330-8503, Japan. FAU - Ishiko, Hiroaki AU - Ishiko H AD - Research & Development Department, Mitsubishi Kagaku Bio-Clinical Laboratories Inc., 3-30-1 Shimura, Itabashi-ku, Tokyo 174-8555, Japan. FAU - Matsuzaki, Yasushi AU - Matsuzaki Y AD - Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan. FAU - Tanaka, Naomi AU - Tanaka N AD - Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan. FAU - Imawari, Michio AU - Imawari M AD - Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A Antigens) RN - 0 (Interferon-alpha) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Binding Sites MH - *Epitopes, T-Lymphocyte MH - HLA-A Antigens/*metabolism MH - Hepacivirus/*immunology MH - Hepatitis C/drug therapy/immunology MH - Humans MH - Interferon-alpha/therapeutic use MH - Interferon-gamma/biosynthesis MH - T-Lymphocytes, Cytotoxic/*immunology EDAT- 2004/05/29 05:00 MHDA- 2004/06/25 05:00 CRDT- 2004/05/29 05:00 PHST- 2004/05/29 05:00 [pubmed] PHST- 2004/06/25 05:00 [medline] PHST- 2004/05/29 05:00 [entrez] AID - 10.1099/vir.0.79801-0 [doi] PST - ppublish SO - J Gen Virol. 2004 Jun;85(Pt 6):1521-1531. doi: 10.1099/vir.0.79801-0.