T-CELL CONTROL OF AUTOREACTIVITY IN SLE

描述：(改编自申请人的摘要)-T细胞调节 自身免疫小鼠产生抗Sm和其他抗核抗体。在……里面 此次竞争性更新，一系列新近衍生的Sm特异性CD4T细胞 我们将利用克隆来了解克隆的特异性和功能 这个SLE模型中的T细胞。细胞因子的产生、TCR基因的使用和特异性 克隆人的数量将会确定。使用这些克隆的TCR数据，转基因 将产生(TG)小鼠，其中T细胞谱系偏向于 SM-认可，首席调查员和他的同事将检查 体液反Sm产生的后果。免疫原性或 免疫优势Sm体内给药的免疫抑制作用 将使用Sm反应性TCR和对照MRL/LPR小鼠来探索多肽。至 自身抗原特异性B细胞对Sm的处理及其对机体免疫功能的影响 抗Sm抗体T细胞谱系、T细胞谱系及其功能 将对免疫球蛋白TG小鼠进行检测。在其他实验中，服用 关于MRL/LPR II类相关多肽的最新数据的优势 MHC分子，针对抗原的自身反应性的证据 将寻找衍生的多肽，并将确定是否 自身免疫的小鼠对这些抗原具有耐受性。最后，独特的反Sm 以CH12B淋巴瘤细胞为模型，检测Sm 加工，它是如何被提呈给Sm抗原特异性T细胞的，以及哪个APC 在Sm处理中最有效。

DESCRIPTION: (Adapted from the applicant's abstract) - T cells regulate the production of anti-Sm and other antinuclear antibodies in autoimmune mice. In this competitive renewal, a series of recently-derived Sm-specific CD4 T cell clones will be exploited in order to understand the specificity and function of T cells in this SLE model. Cytokine production, TCR gene usage, and specificity of the clones will be determined. Using TCR data from these clones, transgenic (tg) mice will be generated in which the T cell repertoire is skewed toward Sm-recognition, and the principal investigator and his colleagues will examine the consequences of humoral anti-Sm production. The immunogenic or immunosuppressive effects of in vivo administration of immunodominant Sm peptides will be explored using Sm-reactive TCR and control MRL/lpr mice. To investigate processing of Sm by autoantigen-specific B cells and its effect on the T cell repertoire, the repertoire and function of T cells from anti-Sm immunoglobulin tg mice will be examined. In additional experiments, taking advantage of recent data concerning peptides associated with MRL/lpr class II MHC molecules, evidence for autoreactivity against the antigens from which the peptides are derived will be sought, and it will be determined whether the autoimmune mice are tolerant to these antigens. Finally, unique anti-Sm transfected CH12 B lymphoma cells will be used as model APC to ask how Sm is processed, how it is presented to Sm-antigen specific T cells, and which APC are most efficient in Sm processing.