Cellular immune response to core region protein of hepatitis C virus in patients with chronic hepatitis C

慢性丙型肝炎患者对丙型肝炎病毒核心区蛋白的细胞免疫反应

基本信息

批准号：
05454245
负责人：
KAKUMU Shinichi
金额：
$ 3.58万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454245/
关键词：
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

项目摘要

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.

有证据表明，针对 HCV 核心蛋白的细胞免疫可能在病毒感染的发病机制中很重要。因此，对来自慢性HCV感染患者的外周血单核细胞产生的IFN-γ进行了检查。使用重组HCV核心融合蛋白评估细胞免疫反应。为了鉴定免疫显性表位，还使用一组覆盖整个核心区域的合成肽评估了应答者中 IFN-γ 的产生。 46 名慢性肝病患者中的 24 名（52%）的单核细胞对核心蛋白有反应；无症状的 HCV 携带者表现出较低的缓解率。与治疗失败的持续肝炎患者相比，接受 IFN-α 治疗并进入临床和病毒学缓解的个体的缓解率更高。在 25 名单核细胞对 HCV 核心蛋白有反应的患者中，18 名对一种或多种肽有显着反应； 12 名患者对含有亲水序列的肽混合物产生反应。核心肽氨基酸序列141-160被9名患者识别。有趣的是，8 名携带 HLA DR 4 和 w53 单倍型的患者中有 7 名识别了肽序列 141-160。因此，单核细胞反应似乎受到 HLA DR 限制，并且反应细胞被鉴定为 CD4+T 细胞。这项研究表明 HCV 核心蛋白内存在与 HLA DR 表型相关的免疫显性 T 细胞表位，并提供了一种研究 CD4+ T 细胞在 HCV 相关肝病发病机制中的作用的方法。