| Project/Area Number |
05454245
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| Research Category |
Grant-in-Aid for General 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 | Nagoya University |
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Principal Investigator |
KAKUMU Shinichi Nagoya University School of Medicine, assistant professor., 医学部, 講師 (10115545)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Akihiko Nagoya University School of Medicine, senior resident., 医学部, 医員
YOSHIOKA Kentaro Nagoya University School of Medicine, lecturer., 医学部, 助手 (60201852)
相山 敏之 名古屋大学, 医学部, 医員
山田 正樹 名古屋大学, 医学部, 医員
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1993: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | hepatitis C virus / core region protein / peripheral blood lymphocyte / immune response / synthetic peptide / T cell epitope / HLA DR / CD4+ T cell / 免疫応答 / インターフェロンガンマ産生 / HLA |
|---|
| Research Abstract |
Evidence suggest that cellular immunity to HCV core protein may be important in the pathogenesis of viral infection. Therefore IFN-gamma production by peripheral blood mononuclear cells derived from patients with chronic HCV infection was examined. The cellular immune response was evaluated with a recombinant HCV core fusion protein. To identify the immunodominant epitopes, IFN-gamma production in responders was also assessed with a panel of synthetic peptides that covered the entire core region. Mononuclear cells from 24 (52%) of 46 patients with chronic liver disease responded to the core protein ; asymptomatic HCV carriers demonstrated a lower response rate. Individuals who had received IFN-alpha treatment and went into clinical and virologic remission had a higher response rate compared to those with ongoing hepatitis who failed therapy. Of 25 patients whose mononuclear cells responded to HCV core protein, 18 had a significant response to one or more peptides ; 12 patients reacted to a peptide mixture containing hydrophilic sequences. The core peptide amino acid sequence 141-160 was recognized by 9 patients. Interestingly, 7 of 8 patients bearing HLA DR 4 and w53 haplotypes recognized the peptide sequence 141-160. Thus, the mononuclear cell response appeared to be HLA DR restricted and the responding cells were identified as CD4+T cells. This study indicates the presence of immunodominant T cell epitopes within HCV core protein in association with HLA DR phenotypes and provides an approach to investigate the role of CD4+ T cells in the pathogenesis of HCV associated liver disease.
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