Structure and Function of the Immunological Synapse

T细胞和APC之间的接触面上蛋白质的特殊排列是已知的 作为免疫突触。突触的确切功能尚不清楚，但已被提出 在TCR信号转导和TCR下调过程中发挥作用。在这里，我们提出了一个模型 提示信号、完全受体磷酸化和信号传导之间存在复杂的关系 降低监管。重新聚集到突触中心促进了受体的全面磷酸化，并完全 磷酸化受体是降解的目标。该模型还表明，受体不能 被招募到突触中心，只被部分磷酸化，并被循环到 去磷酸化后的质膜。在这个应用程序中，我们提出了一系列实验来测试这一点 假设使用最先进的成像技术。具体地说，在具体目标#1中，我们建议分析 突触形成、受体磷酸化与受体降解的关系。具体而言 目的#2，我们建议确定完全磷酸化与部分磷酸化的磷酸化位点 磷酸化受体。在特定的目标#3中，我们建议研究受体下调在 胸腺细胞信号。最后，在具体目标#4中，我们建议研究CD28和CD2在TCR中的作用 回收利用和降解。

The specific arrangement of proteins in the contact surface between the T cell and the APC is known as the immunological synapse. The exact function of the synapse is not clear but it has been proposed to function in the process of TCR signaling and also for TCR downregulation. Here we propose a model that suggests that there is a complex relationship between signaling, full receptor phosphorylation and downregulation. Recruitment to the center of the synapse facilitates full receptor phosphorylation, and fully phosphorylated receptors are targeted for degradation. The model also suggests that receptors that are unable to be recruited to the center of the synapse become only partially phosphorylated and are recycled to the plasma membrane after dephosphorylation. In this application, we propose a series of experiments to test this hypothesis using state of the art imaging techniques. Specifically, in Specific Aim # 1, we propose to analyze the relationship between synapse formation, receptor phosphorylation and receptor degradation. In Specific Aim #2, we propose to determine the site ofphosphorylation of fully phosphorylated versus partially phosphorylated receptors. In Specific Aim #3, we propose to examine the role of receptor downregulation in thymocyte signaling. Lastly, in Specific Aim #4, we propose to examine the role of CD28 and CD2 in TCR recycling and degradation.