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.

我们研究了慢性丙型肝炎患者对丙型肝炎病毒（HCV）核蛋白的T细胞反应，以阐明HCV感染的免疫发病机制。我们证明了HCV感染患者的外周血中存在细胞毒性T淋巴细胞（CTL）。我们成功诱导了HLA B44限制的HCV特异性CTL，并将最小的最佳表位定义为HCV核蛋白残基88至96。我们进一步证明了HCV特异性辅助辅助T细胞存在并刺激了CTLS的激活和刺激。 HCV迅速突变。但被分类为几种基因型。 HCV核蛋白残基的氨基酸序列88至96在HCV分离株中保守除残基91外。残基91的氨基酸在HCV.HLA B44限制的HCV特异性CTL的同一基因型中也保守了II/2A/2A/1BV，也可以识别HCV特异性CTL均未引起II/1BV的HCV特异性CTL。 IV/2B。但是，基因型I/1a的罕见变体HCV可能会诱导HLA B44限制的HCV特异性CTL。该结果不仅有助于阐明HCV感染的免疫致病机制，而且还有助于设计CTL疫苗以防止HCV感染并消除受感染HLA B44患者的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）。

Hiroto Kita: "HLA B44-restricted cytotoxic T lymphocytes recognizing an epitope in hepatitis C virus nucleocapsid protein" Hepatology.

Hiroto Kita：“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中的表位”肝病学。

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)。