Intermolecular Interactions in the Immunological Synapse

FRET显微镜是研究生命中蛋白质与蛋白质相互作用的一种非常有效的手段 细胞本项目使用FRET显微镜来研究TCR之间的诱导相互作用， 和抗原识别过程中出现的辅助受体。FRET显微镜将用于 分析CD 8a β和aa作为共受体和被募集到细胞的不同能力， 免疫突触在抗原识别，以及确定如何内源性 肽增强T细胞识别，包括增强TCR：辅助受体相互作用。的 在抗原识别过程中Lck和Fyn的运动和相互作用将被分析， 荧光嵌合体，并与FRET生物传感器。已发现CDS的差异唾液酸化 在发育中的胸腺细胞和活化的T细胞中。唾液酸化在CDS募集至 将研究突触、链配对、TCR：CD 8和CD 8：Lck相互作用。转基因 表达CD 3C-CFP和CD 8 β-YFP的小鼠将用于TCR：辅助受体相互作用的成像 在胸腺细胞与基质细胞的结合物中，在不同的选择条件下， 条件下，了解TCR：辅助受体相互作用的速度和强度如何 在积极和消极的选择中被调节。这些因素也将被分析为幼稚， 效应和记忆T细胞。T细胞抗原受体、辅助受体 如CD 4和信号蛋白，对免疫反应至关重要。了解如何 这些相互作用的发生将有助于改善对病毒或癌症的免疫应答， 以及减少自身免疫反应。

FRET microscopy is a very effective means to investigate protein:protein interactions in living cells. This project uses FRET microscopy to investigate the induced interactions between TCR and co-receptors that occur during antigen recognition. FRET microscopy will be used to analyze the different abilities of CD8a(3 and aa to act as coreceptors and to be recruited to the immunological synapse during antigen recognition, as well as to determine how endogenous peptides enhance T cell recognition, including enhancing the TCR:coreceptor interaction. The movement and interactions of Lck and Fyn during antigen recognition will be analyzed with fluorescent chimeras, and with a FRET biosensor. Differential sialylation of CDS has been found in developing thymocytes and in activated T cells. The role of sialylation in recruitment of CDS to the synapse, chain pairing, TCR:CD8 and CD8:Lck interactions will be investigated. Transgenic mice expressing CD3C-CFP and CD8(3-YFP will be used to image TCR:coreceptor interactions in cell conjugates between developing thymocytes and stromal cells, under different selecting conditions, to understand how the speed and intensity of the TCR:coreceptor interactions are modulated in positive and negative selection. These factors will also be analyzed for naive, effector and memory T cells. The interactions between the T-cell antigen receptor, coreceptors such as CD4,and signaling proteins, are crucial to the immune response. Understanding how these interactions take place will aid in improving the immune response to viruses or cancer, and in reducing autoimmune reactions.