1993 Fiscal Year Final Research Report Summary
Production of antibodies to inhibit the cytotoxic activities of hepatitis C virus-specific cytotoxic T cells
| Project/Area Number |
03557035
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Jichi Medical School (1993)
The University of Tokyo (1991-1992) |
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Principal Investigator |
IMAWARI Michio Jichi Medical School, Medicine, Professor, 医学部, 教授 (70134228)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Takashi Jichi Medical School, Medicine, Associate, 医学部, 助手 (10254913)
MORIYAMA Takashi Jichi Medical School, Medicine, Assistant Professor, 医学部, 講師 (10240706)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Hepatitis C / Hepatitis C virus / Cytotoxic T cell / T cell receptor / Antibody |
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| Research Abstract |
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.
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