Structure and Function of the Immunological Synapse

免疫突触的结构和功能

• 批准号: 8034681
• 负责人: Andrey S. Shaw
• 金额: $ 27.79万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8034681
• 关键词: Antigens; Applications Grants; Binding; CD28 gene; Cell membrane; Cells; Complex; Data; Down-Regulation; Image; Imaging Techniques; Lead; Ligands; Location; Modeling; PTPN11 gene; PTPN6 gene; Peptides; Phosphoric Monoester Hydrolases; Phosphorylation; Play; Process; Protein Dephosphorylation; Protein Tyrosine Phosphatase; Proteins; Receptor Signaling; Recruitment Activity; Recycling; Role; Series; Signal Transduction; Site; Structure; Surface; Synapses; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Testing; immunological synapse; immunological synapse formation; insight; receptor; receptor downregulation; receptor expression; receptor internalization; receptor recycling; research study; synaptic function; synaptogenesis; thymocyte; trafficking

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.

T细胞和APC之间的接触表面中蛋白质的特定排列是已知的 作为免疫突触。突触的确切功能尚不清楚，但有人提出， 在TCR信号传导过程中起作用，也用于TCR下调。在这里，我们提出了一个模型， 这表明信号传导、完全受体磷酸化和 下调募集到突触中心促进受体完全磷酸化， 磷酸化受体被靶向降解。该模型还表明，不能被激活的受体 被募集到突触中心的蛋白质只被部分磷酸化，并被回收到突触中心。 去磷酸化后的质膜。在这个应用中，我们提出了一系列的实验来测试这一点 假设使用最先进的成像技术。具体而言，在具体目标#1中，我们建议分析 突触形成、受体磷酸化和受体降解之间的关系。在特定 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， 磷酸化受体在具体目标#3中，我们建议检查受体下调在以下方面的作用： 胸腺细胞信号传导最后，在具体目标#4中，我们建议检查CD28和CD2在TCR中的作用。 回收和降解。