Structure and Function of the Immunological Synapse

免疫突触的结构和功能

• 批准号: 7762700
• 负责人: Andrey S. Shaw
• 金额: $ 28.07万
• 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/7762700
• 关键词: Antigens; Applications Grants; Arts; Binding; CD28 gene; Cell membrane; Cells; Complex; Data; Down-Regulation; Face; HC phosphatase; Image; Imaging Techniques; Lead; Ligands; Location; Modeling; PTPN11 gene; Peptides; Phosphoric Monoester Hydrolases; Phosphorylation; Play; Process; Protein Dephosphorylation; 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.

蛋白质在T细胞和APC之间的接触面上的具体排列是已知的