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

Research Project

Project/Area Number 03557035
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionJichi Medical School (1993)
The University of Tokyo (1991-1992)

Principal Investigator

IMAWARI Michio  Jichi Medical School, Medicine, Professor, 医学部, 教授 (70134228)

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)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1993: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1992: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1991: ¥8,300,000 (Direct Cost: ¥8,300,000)
KeywordsHepatitis C / Hepatitis C virus / Cytotoxic T cell / T cell receptor / Antibody / HLAB44 / C型肝炎ウイルスコア抗原
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.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kita,Hiroto: "HLA B44-restricted cytotoxic T lymphocytes recognizing an epitope on hepatitis C virus nucleocapsid protein" Hepatology. 18. 1039-1044 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 井廻道夫: "C型肝炎の細胞性免疫応答" 最新医学. 49. 301-303 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Moriyama T, et al.: "Pathogenesis of and measures for chronic hepatitis. (in Japanese)" Practitioners. 2. 163-169 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Imawari M.: "Mechanisms of cell injury of and measures for viral diseases. (in Japanese)" Medical Practice. 10. 858-863 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kita H, et al.: "HLA B44-restricted cytotoxic T lymphocytes recognizing an epitope on hepatitis C virus nucleocapsid protein." Hepatology. 18. 1039-1044 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Imawari M.: "Cell-mediated immune responce in hepatitis C.(in Japanese)" Saishin-igaku. 49. 301-301 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 森 山 貴 志: "慢性肝炎の発症機序と対策" Practitioners. 2. 163-169 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 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)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kita Hiroto: "HLA B44-restrincted cytotoxic T lymphocytes recognizing sn epitope on hepatitis C virus nucleoc〓sid a protein" Hepatology. 18. 1039-1044 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 井 廻 道 夫: "C型肝炎の細胞性免疫応答" 最新医学. 49. 301-303 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hiroto Kita: "HLA B44-restricted cytotoxic T lymphocytes recognizing an epitope in hepatitis C virus nucleocapsid protein" Hepatology.

    • Related Report
      1992 Annual Research Report
  • [Publications] Michio.Imawari,et al: "Viral hepatitis C,D,and E,ed by Shikata T,Purcell RH and Uchida T.pp69-74 Cytotoxicity of a non-A,non-B hepatitis-specific T-cell clone on hepatocytes from patients with various liver diseases and interferon a-treated hepatocytes from patients with chronic non-A,non-B hepatitis." Elsevier Science Publishiers B.V., (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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