Intermolecular Interactions in the Immunological Synapse

FRET显微镜是研究蛋白质的一种非常有效的手段：生命中的蛋白质相互作用 细胞。这个项目使用FRET显微镜来研究TCR之间的诱导相互作用 以及在抗原识别过程中发生的辅助受体。FRET显微镜将被用于 分析CD8a(3)和AA作为辅助受体并被募集到细胞中的不同能力 抗原识别过程中的免疫突触，以及内源性 多肽增强T细胞识别，包括增强TCR：辅助受体的相互作用。这个 将分析Lck和Fyn在抗原识别过程中的运动和相互作用 荧光嵌合体，并带有FRET生物传感器。发现了CDS的差示唾液酸化反应 在发育中的胸腺细胞和激活的T细胞中。唾液酸化在CDS招募中的作用 将研究突触、链配对、TCR：CD8和CD8：LCK相互作用。转基因 表达cd3c-CFP和CD8(3-YFP)的小鼠将用于成像TCR：辅助受体相互作用 在不同选择下，发育中的胸腺细胞和基质细胞之间的细胞结合 条件，以了解TCR：辅助受体相互作用的速度和强度是如何 调制在正选择和负选择中。这些因素也将被分析为幼稚， 效应器和记忆性T细胞。T细胞抗原受体、辅受体之间的相互作用 如CD4和信号蛋白，对免疫反应至关重要。了解如何 这些相互作用将有助于提高对病毒或癌症的免疫反应， 以及在减少自身免疫反应方面。

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.