RHEUMATOID ARTHRITIS AND LYME DISEASE--T CELL RECEPTOR

T细胞似乎在类风湿的发病机制中起作用 关节炎，尽管还没有T细胞的表现 对假定的疾病相关抗原的反应性。 近几年来对该结构的理解和研究进展 T细胞抗原受体的遗传学已经提供了新的 研究T细胞特异性的方法。在本提案T中 细胞克隆将来自井的滑膜间隙(SS) 类风湿性关节炎患者的定义子集，即典型或明确的类风湿关节炎 增生性滑膜炎。疾病特异性T细胞克隆将是 从从此派生的异类克隆中标识 在找到克隆或寡克隆的基础上发现炎症部位 抗原受体基因重排的分布。T细胞 从SS派生的莱姆关节炎患者会 类似地被研究为疾病相关抗原的模型 是已知的。 白介素2依赖的T细胞克隆 外周血将来自莱姆关节炎患者 和RA。在莱姆关节炎的情况下，T细胞克隆将被培养出来 与病原体伯格多尔费里。此外，T细胞 克隆将与抗T3抗体平行生长，以进一步 确认抗T3抗体能维持抗原- T细胞系在缺乏特异性的情况下生长的特异性 抗原。在RA的情况下，T细胞克隆将仅在 抗T3抗体。利用T细胞受体重排 这些T细胞克隆将通过Southern印迹分析进行研究 (包括阿尔法链的脉冲场电泳法)和 DNA测序。 本提案的长期目标是确定 类风湿关节炎和类风湿性关节炎患者滑膜间隙来源的疾病特异性T细胞 产生针对T细胞的单抗 这些细胞上的受体。这样的抗体将是理论上的， 具有诊断意义，或许还有治疗意义。

T cells appear to play a role in the pathogenesis of rheumatoid arthritis although there has been no demonstration of T cell reactivity to putative disease-related antigens. Recent advances in the understanding of the structure and genetics of the T cell antigen-receptor have made available new approaches to the study of T cell specificity. In this proposal T cell clones will be derived from the synovial space (SS) of a well defined subset of RA patients, i.e. classical or definite RA with proliferative synovitis. The disease-specific T cell clones will be identified from among the heterogeneous clones derived from this site of inflammation on the basis of finding a clonal or oligoclonal distribution of antigen receptor gene rearrangements. T cells derived from the SS of patients with Lyme arthritis will be similarly studied as a model in which the disease related antigen is known. Interleukin-2 dependent T cell clones from the SS and the peripheral blood will be derived from patients with Lyme arthritis and RA. In the case of Lyme arthritis, T cell clones will be grown with the causative agent, B. burgdorferi. In addition, T cell clones will be grown in parallel with anti-T3 antibody to further confirm that anti-T3 antibody can maintain the antigen- specificity of T cell lines grown in the absence of specific antigens. In the case of RA, T cell clones will be grown only with anti-T3 antibody. T cell receptor rearrangements utilized by these T cell clones will be studied by using Southern blot analysis (including pulse-field electrophoresis for the alpha chain) and DNA sequencing. The long-term goal of the present proposal is to identify the disease-specific T cells derived from the synovial space in RA and generate monoclonal antibodies directed toward the T cell receptor on such cells. Such antibodies would be of theoretical, diagnostic, and perhaps therapeutic significance.