Production of antibodies to inhibit the cytotoxic activities of hepatitis C virus-specific cytotoxic T cells

生产抑制丙型肝炎病毒特异性细胞毒性 T 细胞细胞毒活性的抗体

基本信息

批准号：
03557035
负责人：
IMAWARI Michio
金额：
$ 8.38万
依托单位：
Jichi Medical School (1993)The University of Tokyo (1991-1992)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03557035/
关键词：
Hepatitis C Hepatitis C virus Cytotoxic T cell T cell receptor Antibody HLAB44 C型肝炎ウイルスコア抗原

项目摘要

To elucidata the pathogenesis of hepatitis C and apply them to the treatment, we planned to produce antibodies to the variable regions or antigen-binding regions of the T cell receptor of hepatitis C virus-specific cytotoxic T cells to inhibit the cytotoxic activities. We screened cDNA library of a T cell clone TA-NB-2 to obtain the cDNA of T cell receptor beta chain. The TA-NB-2 cells lysed hepatocyts from patients with hepatitis C in an HLA-unrestricted manner. It turned out to be that there existed at least 3 different T cell receptors in TA-NB-2 cells, suggestig that they were not monoclonal. Then we studied the T cell receptor usage of liver infiltrating T cells of hepatitis C patients. We established T cell clones from the liver infiltrating T cells of 5 patients with hepatitis C.In one patients, Vbeta2, Vbeta6.1-3, and Vbeta7 were used preferentially. We also generated HLA B44-restricted cytotoxic T cells recognizing hepatitis C virus core antigen amino acid reidues 88 to 96 from peripheral blood lymphocytes of a patient with hepatitis C.We succeeded in cloning the HLA B44-restricted hepatitis C virus-specific cytotoxic T cells. We will analyze the T cell receptor, clone the cDNA of T cell receptor, express the T cell receptor, and generate the antibodies to inhibit the cytotoxic activities of the cytotoxic T cell clones by binding to the T cell receptor.

为了elucidata丙型肝炎的发病机理并将其应用于治疗，我们计划对乙型肝炎病毒特异性细胞毒性T细胞的T细胞受体的可变区域或抗原结合区域产生抗体，以抑制细胞毒性活性。我们筛选了T细胞克隆TA-NB-2的cDNA库，以获得T细胞受体β链的cDNA。 TA-NB-2细胞以HLA无限制的方式裂解来自丙型肝炎患者的肝细胞。事实证明，在TA-NB-2细胞中至少存在至少3个不同的T细胞受体，这表明它们不是单克隆人。然后，我们研究了肝炎患者的肝脏浸润T细胞的T细胞受体使用。我们优先使用了5例丙型肝炎患者的肝脏浸润T细胞的T细胞克隆。我们还从外周血血液淋巴细胞中识别出乙型肝炎的HLA B44限制性细胞毒性T细胞88至96乙型肝炎。我们成功地克隆了HLA B44限制性肝炎的HLA B44限制性肝炎病毒毒素细胞。我们将分析T细胞受体，克隆T细胞受体的cDNA，表达T细胞受体，并产生抗体，以通过与T细胞受体结合来抑制细胞毒性T细胞克隆的细胞毒性活性。