Jones D E, Palmer J M, Yeaman S J, Bassendine M F, Diamond A G
Department of Medicine, University of Newcastle, Newcastle-upon-Tyne, UK.
Clin Exp Immunol. 1997 Mar;107(3):562-8. doi: 10.1046/j.1365-2249.1997.3101202.x.
The study of T cell responses to autoantigens in human autoimmunity has been hampered by difficulties, firstly in identifying significant autoantigens, and secondly in the purification of authentic human proteins in sufficient quantities to allow characterization of antigen-specific T cell responses. In this study we have purified a human autoantigen, pyruvate dehydrogenase, retaining its enzymatic activity, and characterized autoreactive T cell responses to it in a human autoimmune disease, primary biliary cirrhosis. T cell responses to a mixture of the E2 and protein X subunits of human pyruvate dehydrogenase complex are seen in most affected patients, but in only a small minority of normal and chronic liver disease controls. By contrast, responses to whole pyruvate dehydrogenase complex occur with equal frequency in both groups. This suggests that responses to the E2 component/protein X of pyruvate dehydrogenase complex play a role in the pathogenesis of primary biliary cirrhosis. The availability of significant quantities of the human autoantigen in primary biliary cirrhosis makes this condition an interesting model in which to study true autoreactive human T cell responses.
在人类自身免疫性疾病中，对自身抗原的T细胞反应研究一直受到重重困难的阻碍，首先是难以识别重要的自身抗原，其次是难以纯化出足够量的纯正人类蛋白质以表征抗原特异性T细胞反应。在本研究中，我们纯化了一种人类自身抗原——丙酮酸脱氢酶，并保留了其酶活性，还在一种人类自身免疫性疾病——原发性胆汁性肝硬化中，对针对该抗原的自身反应性T细胞反应进行了表征。在大多数患病患者中都能观察到对人类丙酮酸脱氢酶复合物E2和蛋白X亚基混合物的T细胞反应，但在正常人和慢性肝病对照者中只有一小部分人有这种反应。相比之下，两组中对完整丙酮酸脱氢酶复合物的反应频率相同。这表明对丙酮酸脱氢酶复合物E2成分/蛋白X的反应在原发性胆汁性肝硬化的发病机制中起作用。在原发性胆汁性肝硬化中可获得大量的人类自身抗原，这使得该疾病成为研究真正的人类自身反应性T细胞反应的一个有趣模型。
