The analysis of epitope and immunological response of primary biliary cirrhosis

原发性胆汁性肝硬化的表位及免疫反应分析

• 批准号: 11470124
• 负责人: HAYASHIDA Kazuhiro
• 金额: $ 9.28万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470124/
• 关键词: Primary Biliary Cirrhosis; autoimmune; autoantibody; auto-reactive T cell; molecular mimicry; analogue peptide; autoantigen; anti-mitochondria antibody; 自己免疫性疾患; 免疫応答; ペプチド; MHC複合体; T細胞エピトープ; ミトコンドリア抗原

The pyruvate dehydrogenase E2 component (PDC-E2) is a major antigen for the anti-mitochondria antibody that is a specific autoantibody associated with primary biliary cirrhosis. We have clarified that the major T cell epitope is PDC-E2 163-176 (163 GDLLAEIETDKATI 176), the important site of T cell recognition is 170E, 172D and 173K (ExDK sequence), and the some of human PDC-E2 reactive T cell clones (hPDC-TCC) cross-react with the E-coli PDC-E2 antigen.(Year 1999) The All hPDC-TCC restricted by HLA-DR53 were Th1 type helper T cell, and they reacted not only with the E-coli derived peptide which resembled the molecular mimicry for human PDC-E2 but also the other bacteria derived peptides.(Year 2000) The hPDC-TCC was classified into two groups according to the reactive pattern for the foreign antigen and the autoantigens. The one was the clones that reacted only with the autoantigen of human mitochondria derived proteins, and the other was the clones that reacted not only with the autoantigens but also with the many bacteria derived peptide contained the ExDK motif in the sequence.(Year 2001) Some of the hPDC-TCC cross-reacted with the nuclear antigens, and the clones specific for E-coli OGDC-E2 34-47 also cross-reacted with the human mitochondria autoantigens.We have clarified the existence of cross reactivity of T cell between autoantigens and foreign antigens, and suggested the possibility of molecular mimicry regarding the break of tolerance for the autoantigens.

丙酮酸脱氢酶E2组分（PDC-E2）是抗线粒体抗体的主要抗原，抗线粒体抗体是与原发性胆汁性肝硬化相关的特异性自身抗体。我们已经阐明，主要的T细胞表位是PDC-E2 163-176（163 GDLLAEIETDKATI 176），T细胞识别的重要位点是170 E，172 D和173 K（ExDK序列），并且一些人PDC-E2反应性T细胞克隆（hPDC-TCC）与E-coli PDC-E2抗原交叉反应。(Year HLA-DR 53限制性hPDC-TCC均为Th 1型辅助性T细胞，不仅与大肠杆菌衍生肽（类似于人PDC-E2的分子模拟物）反应，而且与其他细菌衍生肽反应。(Year 2000）根据对外源抗原和自身抗原的反应模式将hPDC-TCC分为两组。一个是仅与人线粒体衍生蛋白的自身抗原反应的克隆，另一个是不仅与自身抗原反应，而且与序列中含有ExDK基序的许多细菌衍生肽反应的克隆。(Year 2001）部分hPDC-TCC与核抗原发生交叉反应，E-coliOGDC-E234 -47特异性克隆与人线粒体自身抗原也发生交叉反应，阐明了自身抗原与外源抗原在T细胞上的交叉反应性，并提出了破坏自身抗原耐受性的分子模拟的可能性。

项目成果

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