CD3 e functions in T cells

6.项目摘要 T细胞受体是一种多亚基受体复合物，有四种蛋白质参与其中， 细胞内信号转导迄今为止，几乎所有的研究都集中在一个信号上， 基序是所有四个亚基共有的。我们提供了第二次的初步证据 信号基序，仅存在于四条链之一，CD 3 β链中。我们 术语这个序列的基本丰富的伸展，并已确定，它可以与一个相互作用， 丝氨酸/苏氨酸激酶称为GRK 2，也可以与磷脂相互作用。 我们将通过修改它来描述这个基本的丰富延伸的功能作用， 表征这些修饰对1）T细胞受体和趋化因子 受体串扰，2）磷脂相互作用，和3）T细胞发育和T细胞 效应器功能。 我们的研究结果将为T细胞功能提供新的机制见解 在正常和异常的免疫反应。新的治疗策略 干预T细胞功能的可能性。

6. Project Summary The T cell receptor is a multi-subunit receptor complex with four proteins involved in intracellular signal transduction. Almost all studies to date have focused on a signaling motif that is common to all four subunits. We provide preliminary evidence of second signaling motif that is only present in one of the four chains, the CD3 epsilon chain. We term this sequence the basic rich stretch, and have determined that it can interact with a serine/threonine kinase termed GRK2, and can also interact with phospholipids. We will delineate the functional role of this basic rich stretch by modifying it and characterizing the effects of these modifications on 1) T cell receptor and chemokine receptor cross-talk, 2) phospholipid interactions, and 3) T cell development and T cell effector functions. The findings from our studies will yield new mechanistic insights into T cell functions during normal and abnormal immune responses. Novel therapeutic strategies for intervening in T cell functions could emanate from our studies.