NEUROMUSCLUAR IMMUNOPATHOLOGY IN EAMG-RESISTANT RATS

Gravis（EAMG），两种辅助性T细胞之间的免疫学差异 近亲繁殖的大鼠品系一方面解释了疾病的易感性 (in刘易斯大鼠）和抗病性（Wistar Furth 大鼠）。 这些研究的工作假设是T细胞 Wistar Furth大鼠的隔室可能缺乏激活能力， 现有B细胞的反应性，这些细胞有可能产生 致病抗体;这种质量可能与缺乏T 细胞对AChR α内所含表位的反应性 在刘易斯中显示免疫优势的亚基序列α 100-116 大鼠 研究将包括对抗体介导的 通过消除这种T细胞诱导的神经肌肉功能障碍 新生儿耐受诱导和肽诱导刘易斯大鼠的反应性 封锁战略。 拟议的研究还将评估 Wistar Furth T细胞特异性库中的这种缺陷， 将α 100-116应答细胞的频率与 在刘易斯反应中观察到的频率;纳入本评价 将测试WF抗原呈递细胞结合和 α 100-116肽可能是导致 Wistar Furth T细胞不能驱动抗AChR抗体应答 有致病的可能

Gravis (EAMG), immunological differences between helper T cells from two inbred rat strains that explain disease susceptibility on the one hand (in Lewis rats) and disease-resistance on the other hand (in Wistar Furth rats). The working hypothesis for these studies is that the T cell compartment in Wistar Furth rats may lack the ability to activate responsiveness by existing B cells that have the potential to produce disease-causing antibodies; this quality may be related to a lack of T cell reactivity toward an epitope(s) contained within the AChR alpha subunit sequence alpha 100-116 that demonstrates immunodominance in Lewis rats. Studies will include an evaluation of effects on antibody-mediated inducible neuromuscular dysfunction by the elimination of this T cell reactivity in Lewis rats by neonatal tolerance induction and peptide blocking strategies. Proposed studies will also evaluate the importance of this deficit in the Wistar Furth T cell specificity repertoire by comparing the frequency of alpha 100-116 responding cells to the frequency observed in the Lewis response; included in this evaluation will be tests for the ability of WF antigen presenting cells to bind and present the alpha 100-116 peptide that may be responsible for the inability of Wistar Furth T cells to drive an anti-AChR antibody response with disease-causing potential.