DIFFERENTIAL ACTIVATION OF CD4+ T CELL SUBSETS

不同的产生亮氨酸的CD 4 T细胞亚群的产生受T细胞受体强度的影响 介导的信号传导。Th 1/Th 2细胞分化的信号强度模型预测高亲和力 TcR与其配体之间的相互作用将诱导Th 1细胞，低亲合力相互作用将诱导Th 2细胞。 该提案的总体目标是确定TcR连接与不同的TcR连接如何启动信号通路。 亲和肽影响Th 1和Th 2分化的发育调节， 预先存在的细胞因子微环境。该实验室以前的研究表明， TcR信号复合物在分化和定型Th 1和Th 2细胞中的作用不同。我们假设T细胞可能 通过改变大分子信号传导的组成来区分不同的效力信号 这些复合物将调节T细胞活化的结果。在目标1中，我们将定义 在T细胞活化之前、期间和之后，Thl和Th 2细胞中的信号传导复合物，并确定这些信号传导复合物如何在T细胞活化之前、期间和之后产生。 在分化和/或活化期间组装组件。在目标2中，我们将确定是否未能 在强TcR信号传导后诱导Th 2分化是由于抑制Th 2产生信号，通过研究 Th 2相关转录因子的调节和结合。了解与Thl相关的因素， 在细胞因子微环境不起主导作用的情况下，Th 2应答与我们的研究有关。 对过敏性炎症的理解。

The generation of distinct cytokine-producing CD4 T cell subsets is influenced by the strength of T cell receptor mediated signaling. The signal strength model for Thl/Th2 cells differentiation predicts that high avidity interactions between a TcR and its ligand will induce Thl cells and low avidity interactions will induce Th2 cells. The overall goal of this proposal is to determine how signaling pathways initiated by TcR ligation with differing affinity peptides affect the developmental regulation of Thl and Th2 differentiation in the absence of a dominant pre-existing cytokine microenvironment. Previous studies in this laboratory have shown that the organization of the TcR signaling complex in differentiatingand committed Thl and Th2 cells differs. We hypothesize that T cells may discriminate between different potency signals by altering the composition of the macromolecular signaling complexes which will regulate the outcome of T cell activation. In Aim 1, we will define the components of the signaling complexes in Thl and Th2 cells before, during, and after T cell activation and determine how these components are assembled during differentiation and/or activation. In Aim 2, we will determine if the failure to induce Th2 differentiation following strong TcR signaling is due to signals that inhibit Th2 generation by studying the regulation and binding of Th2 associated transcription factors. Understanding the factors that related Thl and Th2 responses in situations in which the cytokine microenvironment does not play a dominant role is relevant to our understanding of allergicinflammation.