Identification of novel hepatitis C virus-specific cytotoxic T lymphocyte epitopes by ELISpot assay using peptides with human leukocyte antigen-A*2402-binding motifs

Identification of novel hepatitis C virus-specific cytotoxic T lymphocyte epitopes by ELISpot assay using peptides with human leukocyte antigen-A*2402-binding motifs
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DOI:
10.1099/vir.0.79801-0
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发表时间:
2004-06-01
影响因子:
3.8
通讯作者:
Imawari, M
Imawari, M
中科院分区:
医学3区
文献类型:
--
作者:
Hakamada, T;Funatsuki, K;Imawari, M

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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 1 b 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 HICV-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.