CO-STIMULATION OF T LYMPHOCYTES BY CD28

描述：（改编自申请人的摘要和具体目标。） T细胞对抗原的应答激活依赖于对T细胞的刺激。 T细胞抗原受体和通过辅助T细胞传递的信号 细胞分子，如CD 28。CD 28结合B7（CD 80）和B7-2（B70）， 由抗原呈递细胞表达的细胞表面分子。的 本申请试图定义CD 28的结构基础， 介导的信号传导，目的是阐明 信号通路和细胞反应之间的联系以前的研究 已经表明CD 28的扰动会诱导其酪氨酸 磷酸化第一个具体目标是表征CD 28- 介导的信号需要胞质酪氨酸残基。CD28 用Phe替换Tyr的突变体将用于确定 Tyr残基是CD 28诱导特定的早期免疫应答所必需的。 信号事件和介导某些细胞反应。此外，本发明还提供了一种方法， 与CD 28相互作用需要这些Tyr残基的蛋白质将 被识别。此外，在Tyr 170处结合CD 28并在Tyr 170处结合CD 28的50 kD蛋白质是 与磷脂酰肌醇3 '-激酶p85密切相关， 表征了第二个具体目标是确定 CD 28与p72 itk/emt的相互作用，p72 itk/emt是一个TEC成员， 家族蛋白酪氨酸激酶。第三个具体目标将使用 酵母双杂交系统，以确定蛋白质，可以相互作用， CD 28的胞质结构域独立于其磷酸化。

DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) T-cell activation in response to antigen depends upon stimulation of the T cell antigen receptor and upon signals delivered through accessory T cell molecules, such as CD28. CD28 binds B7 (CD80) and B7-2 (B70), cell-surface molecules expressed by antigen-presenting cells. The current application seeks to define the structural basis for CD28- mediated signaling, with the goal of shedding light on the relationships between signaling pathways and cellular responses. Previous studies have shown that perturbation of CD28 induces its tyrosine phosphorylation. The first specific aim is to characterize the CD28- mediated signals that require cytoplasmic tyrosine residues. CD28 mutants with Phe for Tyr substitutions will be used to determine which Tyr residues are required in order for CD28 to elicit particular early signaling events and to mediate certain cellular responses. In addition, proteins whose interaction with CD28 requires these Tyr residues will be identified. Also, a 50 kD protein that binds CD28 at Tyr 170 and is closely related to phosphatidylinositol 3'-kinase p85 will be characterized. The second specific aim is to determine the importance of the interaction of CD28 with p72itk/emt which is a member of the tec family protein tyrosine kinases. The third specific aim will use a yeast two hybrid system to identify proteins that can interact with the cytoplasmic domain of CD28 independently of its phosphorylation.