RHEUMATOID ARTHRITIS AND LYME DISEASE--T CELL RECEPTOR

T细胞似乎在类风湿性关节炎的发病机制中发挥作用 关节炎，虽然没有证据表明T细胞 对推定的疾病相关抗原的反应性。 对结构的认识和 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。 在本提案中，T 细胞克隆将从孔的滑膜间隙（SS）中获得 RA患者的定义子集，即典型或明确的RA伴 增生性滑膜炎 疾病特异性T细胞克隆将被 从来源于此的异源克隆中鉴定出 炎症部位的基础上找到一个克隆或寡克隆 抗原受体基因重排的分布。 T细胞 来自莱姆关节炎患者的SS将是 类似地作为模型进行研究，其中疾病相关抗原 是已知的。 来自SS和T细胞的白细胞介素-2依赖性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细胞克隆将生长 与病原体B接触。burgdorferi。 此外，T细胞 克隆将与抗T3抗体平行生长，以进一步 证实抗T3抗体可维持抗原- 特异性T细胞系生长在缺乏特异性 抗原 在RA的情况下，T细胞克隆将仅在具有以下条件的情况下生长： 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α链的脉冲场电泳）和 DNA测序 本提案的长期目标是确定 来源于RA滑膜间隙的疾病特异性T细胞， 产生针对T细胞的单克隆抗体 这些细胞上的受体。 这种抗体是理论上的， 诊断，也许还有治疗意义。

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.