T-CELL CONTROL OF AUTOREACTIVITY IN SLE

描述：（改编自申请人的摘要）- T 细胞调节 在自身免疫小鼠中产生抗 Sm 和其他抗核抗体。在 这种竞争性更新，一系列最近衍生的 Sm 特异性 CD4 T 细胞 将利用克隆来了解其特异性和功能 该 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 将确定克隆的数量。使用来自这些克隆的 TCR 数据，转基因 (tg) 将产生 T 细胞库偏向于的小鼠 Sm-识别，首席研究员和他的同事将检查 体液抗 Sm 产生的后果。免疫原性或 免疫显性 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 小鼠来探索肽。至 研究自身抗原特异性 B 细胞对 Sm 的加工及其对 T 细胞库，来自抗 Sm 的 T 细胞的库和功能 将检查免疫球蛋白转基因小鼠。在额外的实验中，采取 关于与 MRL/lpr II 类相关的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 将寻找衍生的肽，并确定是否 自身免疫小鼠对这些抗原具有耐受性。最后，独特的抗Sm 转染CH12 B淋巴瘤细胞作为APC模型，询问Sm如何 处理，如何将其呈递给 Sm 抗原特异性 T 细胞，以及哪种 APC 在 Sm 加工中效率最高。

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.