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

基本信息

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

项目摘要

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成分（PDC-E2）是抗七个抗体的主要抗原，是与原代胆道肝硬化相关的特定自身抗体。我们已经澄清说，主要的T细胞表位是PDC-E2 163-176（163 GDLLAEEITDKATI 176），T细胞识别的重要部位是170E，172D和173K（EXDK序列），以及与人类PDC-E2反应性T细胞控制器（HPDC-TCC）Cross-ec-cross-ec-cross-ec-cross-ec-Crolict pdc pdc pdc pdc pdc pdc pd pdc pd pdc pd pdc pd pd pdc pd pd pd pd pd pd pd。所有受HLA-DR53限制的HPDC-TCC都是Th1型辅助T细胞，它们不仅与E-Coli衍生的肽反应，类似于人类PDC-E2的分子模拟物，还与其他细菌衍生的细菌相似，而且还衍生出的其他细菌。（2000年）（2000年）将HPDC-TCC分类为两种远古犬，并将其分类为两种反复的模式。 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也与人线粒体自身抗原进行了交叉反应。我们已经阐明了自身抗原和外抗原之间T细胞的交叉反应性的存在，并提出了关于自身抗原耐受性破裂的分子模仿的可能性。