Analysis of experimental autoimmune myositis and its immunotherapy

为了解人类多发性肌炎的发病机制，用部分纯化的肌球蛋白免疫刘易斯大鼠，诱导实验性自身免疫性肌炎（EAM），并通过CDR 3谱分析EAM诱导T细胞的T细胞受体（TCR）性质。结果显示，在EAM过程中，肌肉浸润T细胞的TCR V β 8.2、10和12寡克隆扩增。我们目前正在研究通过将这些V β的全长插入表达载体制备的DNA疫苗的预处理是否抑制EAM的发展。我们还试图鉴定部分纯化的肌球蛋白制剂中的主要肌成丝抗原。为此目的，部分纯化的肌球蛋白进一步纯化的层析技术，以纯化肌球蛋白和C-蛋白。免疫与t C-蛋白诱导严重的EAM，而纯化的肌球蛋白只产生轻微的病变的肌肉。这一发现表明，C蛋白，而不是肌球蛋白，是主要的肌生蛋白抗原。

In order to know the pathogenesis of human polymyositis, experimetal autoimmune myositis (EAM) was induced in Lewis rats by immunization with partially purified myosin and the nature of T cell receptor (TCR) of EAM-inducing T cells was analyzed by CDR3 spectratyping. It was revealed that TCR Vbeta8.2, 10 and 12 of muscle-infiltrating T cells was oligoclonally expanded during the course of EAM.We are currently investigating whether pretreatment with DNA vaccines which are prepared by inserting full length of these Vbetas into the expression vector suppresses the development of EAM.We have also tried to identify the major myositogenic antigen in the partially purified myosin preparation. For this purpose, partially purified myosin was further purified by the chromatographic techniques into purified myosin and C-protein. Immunization with t C-protein induced severe EAM, whereas that with purified myosin produced only mild lesions in the muscle. This finding indicates that C-protein, but not myosin, is the major myositogenic antigen.