Studies on the Immunopathogenesis of Viral Hepatitis C

丙型肝炎病毒免疫发病机制的研究

• 批准号: 04454241
• 负责人: IMAWARI Michio
• 金额: $ 3.84万
• 依托单位: Jichi Medical School (1993-1994)The University of Tokyo (1992)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454241/
• 关键词: hepatitis C virus; cytotoxic T cell; HLA B44; antigen epitope; helper T cell; C型肝炎; HLAB44; C型肝炎ウイルスコア抗原

We studied on T-cell responses to hepatitis C virus (HCV) nucleoprotein in patients with chronic hepatitis C to clarify the immunopathogenic mechanisms of HCV infection. We demonstrated the presence of cytotoxic T lymphocytes (CTLs) in peripheral blood of patients with HCV infection. We successfully induced HLA B44-restricted HCV-specific CTLs and defined the minimal optimal epitope to be HCV nucleoprotein residues 88 to 96. We further demonstrated that HCV-specific helper T cells existed and stimulated activation and proliferation of CTLs. HCV mutates rapidly. but is classified into several genotypes. An amino acid sequence of HCV nucleoprotein residues 88 to 96 is conserved among HCV isolates except for residue 91. An amino acid at residue 91 is also conserved among the members of the same genotype of HCV.HLA B44-restricted HCV-specific CTLs could be induced by and recognized HCV of genotypes II/1b and III/2a, but neither I/1a nor IV/2b. A rare variant HCV of genotype I/1a, however, could induced HLA B44-restricted HCV-specific CTLs. The results contribute not only to elucidationof the immunopathogenic mechanisms of HCV infection but also to designing CTL vaccines to prevent HCV infection and eliminate HCV from infected patients with HLA B44.

为探讨丙型肝炎病毒（HCV）感染的免疫致病机制，我们研究了慢性丙型肝炎患者T细胞对HCV核蛋白的反应。我们证明了HCV感染患者外周血中存在细胞毒性T淋巴细胞（CTL）。我们成功地诱导了HLA B44限制性HCV特异性CTL，并将最小最佳表位确定为HCV核蛋白残基88至96。我们进一步证明了HCV特异性辅助性T细胞的存在并刺激CTL的活化和增殖。HCV突变迅速。但被分为几种基因型。HCV核蛋白残基88至96的氨基酸序列在HCV分离株中除了残基91之外是保守的。HLA-B44限制性CTL可被II/1b和III/2a型HCV诱导并识别，但不能被I/1a和IV/2b型HCV识别。然而，一种罕见的I/1a型变异型HCV可诱导HLA-B44限制性HCV特异性CTL。这些结果不仅有助于阐明HCV感染的免疫致病机制，而且有助于设计CTL疫苗预防HCV感染和从HLA-B44感染者体内清除HCV。

项目成果

井廻道夫: "ウイルス性疾患の細胞障害機序とその対策" Medical Practice. 10. 858-863 (1993)

Michio Imawari：“病毒性疾病的细胞毒性机制及其对策”医学实践10。858-863（1993）。

井廻道夫: "C型肝炎の細胞性免疫応答" 最新医学. 49. 301-303 (1994)

Michio Imawari：“丙型肝炎中的细胞介导的免疫反应”《现代医学》49. 301-303 (1994)。

森山貴志: "トランスジェニックマウスを用いた肝障害発症機序の研究" 実験医学. 10. 139-169 (1992)

森山隆：“利用转基因小鼠研究肝损伤机制”《实验医学》10。139-169（1992）。

森山貴志: "慢性肝炎の発症機序と対策" Practitioners. 2. 163-169 (1993)

森山隆：《慢性肝炎发病机制及对策》2. 163-169 (1993)。

Kita.Hiroto: "HLA B44-restricted cytotoxic T lymphocytes recognizing an epitope on hepatitis C virus nucleocapsid protein" Hepatology. 18. 1039-1044 (1993)

Kita.Hiroto：“HLA B44 限制性细胞毒性 T 淋巴细胞识别丙型肝炎病毒核衣壳蛋白上的表位”肝病学。