SELF PEPTIDES BOUND TO MHC CLASS II IN T CELL SELECTION

描述(改编自调查人员的摘要)：CD4+T细胞发挥着 在免疫反应的诱导和调节中起关键作用。这些细胞 识别与表面II类分子络合的多肽 抗原提呈细胞(APC)。大多数MHC II类分子是 由源自“自身”蛋白质的多肽占据。T细胞在中国的发育 胸腺涉及抗原特异性T细胞受体(TCR)与 胸腺皮质上皮细胞和骨髓表达的MHC分子 派生的APC。胸腺自身MHC与TCR的结合可能导致 自身MHC限制性T细胞的正选择，或负选择， 导致携带高亲和力TCR的未成熟T细胞的缺失 自体多肽：MHC。缺乏适用于阳性反应的MHC配体 选择导致胸腺细胞进一步分化受阻 细胞死亡。本项目的总体目标是了解 “自体”多肽在发育中有三个部分：CD4+T细胞。首先，什么？ 是否表达了与MHC II类分子结合的自体多肽 胸腺皮质上皮细胞和骨髓来源的APC？第二, II类多肽谱系在正选择中的作用是什么？ T细胞在体内吗？第三，特定的“自我”多肽在体内的作用 T细胞的阳性选择？为了进行这些研究，他们将建立 与特定的II类相关的“自我”多肽的广泛数据库 分子，并评价它们在选择CD4+T细胞方面的贡献。 这将通过使用TCR转基因小鼠和克隆来促进 针对两个定义肽的抗体：组合的II类复合体 突变的小鼠具有严重改变的“自我”II类指令表 结合多肽。

DESCRIPTION (Adapted from the Investigator's abstract): CD4+ T-cells play a key role in the induction and regulation of immune responds. These cells recognize peptides complexed with class II molecules on the surface of antigen-presenting cells (APC). The majority of MHC class II molecules are occupied by peptides derived from "self" proteins. T-cell development in the thymus involves interaction of Ag-specific T-cell receptors (TCRs) with MHC molecules expressed by thymic cortical epithelial cells and bone marrow derived APC. The engagement of TCR by self MHC in the thymus may lead to positive selection of self-MHC-restricted T-cells, or to negative selection, resulting in deletion of immature T-cells bearing TCRs with a high affinity for self peptide:MHC. The lack of appropriate MHC ligands for positive selection causes arrest of further differentiation of thymocytes followed by cell death. The overall goal of this project is to understand the role of "self" peptides in the development of CD4+ T-cells three parts. First, what are repertoires of self peptides bound to MHC class II molecules expressed in thymic cortical epithelial cells and in bone marrow derived APC? Second, what is the role of the class II:peptide repertoire in positive selection of T-cells in vivo? Third, what is the role of specific "self" peptides in the positive selection of T-cells? To carry out these studies they will build an extensive database of "self" peptides associated with a specific class II molecule and evaluate their contribution to the selection of CD4+ T-cells. These will be facilitated by the use of TCR transgenic mice and monoclonal antibodies specific for two define peptide:class II complexes in combination with mutant mice with severely altered repertoires of "self" class II binding peptides.