SELF PEPTIDES BOUND TO MHC CLASS II IN T CELL SELECTION

描述（改编自研究者摘要）：CD4+ T细胞发挥着重要作用。 在诱导和调节免疫应答中起关键作用。 这些细胞 识别与表面II类分子复合的肽， 抗原呈递细胞（APC）。 大多数MHC II类分子是 由来自“自身”蛋白质的肽占据。 T细胞发育 胸腺涉及Ag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 APC衍生 胸腺中自身MHC与TCR的结合可能导致 自身MHC限制性T细胞的阳性选择，或阴性选择， 导致携带高亲和力TCR的未成熟T细胞的缺失 对于自身肽：MHC。 缺乏合适的MHC配体， 选择导致胸腺细胞进一步分化的停滞， 细胞死亡 本项目的总体目标是了解 “自体”肽在CD4+ T细胞的发育中起三个部分的作用。 首先， 是与表达的MHC II类分子结合的自身肽的库 在胸腺皮质上皮细胞和骨髓来源的APC？ 第二、 II类肽库在正选择中的作用是什么？ 体内T细胞？ 第三，特定的“自我”肽在免疫系统中的作用是什么？ T细胞的阳性选择 为了进行这些研究，他们将建立 一个广泛的数据库的“自我”肽与特定的第二类 分子，并评估它们对CD4+ T细胞选择的贡献。 这些将通过使用TCR转基因小鼠和单克隆抗体来促进。 对两种肽特异性的抗体定义：组合的II类复合物 与突变小鼠严重改变的“自我”II类 结合肽。

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.