LFA-1-MEDIATED COSTIMULATION

描述：抗原呈递给T细胞需要形成稳定的 抗原呈递细胞（APC）是T细胞和抗原呈递细胞（APC）之间的复合物。形成 这种复合物的稳定性受粘附分子的控制， 特别是LFA-1。该复合物提供细胞间和细胞内 蛋白质：蛋白质相互作用发生是必要的T细胞 activation.调查人员的初步结果显示，除了其 LFA-1作为一种粘附分子，可以作为一种共刺激分子发挥作用。 LFA-1对T细胞活化的这种功能性作用可以通过免疫组织化学检测。 诱导IL-2基因表达和下调继发性IL-4 应答此外，LFA-1的共同参与可以改变细胞的组成。 募集到在T细胞位点形成的粘附复合物的蛋白质：APC 互动此应用程序的总体目标是确定 这些蛋白质的募集，或LFA-1在指导这些蛋白质的合成中的可能作用。 粘附复合物内蛋白质的组织，对粘附复合物的影响 LFA-1的共刺激功能。他们将剖析 CD18胞质尾部的特征，其通过以下方式赋予LFA-1的各种功能： 定点诱变和基因转移。通过分离具体职能， 他们希望能辨别出粘附的结构组织是否 复合物在LFA-1功能和T细胞活化中起着不可或缺的作用。 将军他们将通过三个具体目标来实现这一目标： 目的1：确定LFA-1介导T细胞增殖的结构特征 共刺激 目的2：确定LFA-1在T细胞结构组织中的作用 细胞：APC粘附复合物。 目的3：确定β 1（VLA-4）和β 2（LFA-1）整联蛋白是否 在T细胞共刺激中功能等同。

DESCRIPTION: Antigen presentation to T cells requires the formation of a stable complex between the T cell and an antigen presenting cell (APC). The formation of and stability of this complex is controlled by adhesion molecules, most notably LFA-1. This complex provides for both intercellular and intracellular protein:protein interactions to take place that are essential to T cell activation. The investigators' preliminary results show that in addition to its role as an adhesion molecule, LFA-1 can function as a costimulatory molecule. This functional effect of LFA-1 on T cell activation can be detected by the induction of IL-2 gene expression and the down regulation of secondary IL-4 responses. In addition, co-engagement of LFA-1 can alter the composition of proteins recruited to the adhesion complex that forms at the site of T cell:APC interaction. The overall goal of this application is to determine whether the recruitment of these proteins, or the possible role of LFA-1 in directing the organization of proteins within the adhesion complex, impacts on the costimulatory function of LFA-1. They will dissect the distinct structural features of the CD18 cytosolic tail that impart various functions of LFA-1 by site directed mutagenesis and gene transfer. By segregating specific functions, they hope to discern whether the structural organization of the adhesion complex plays an integral role in LFA-1 function and in T-cell activation in general. They will do this through three Specific Aims: Aim 1: Determine the structural features of LFA-1 that mediate T cell costimulation. Aim 2: Determine the role of LFA-1 in the structural organization of the T cell:APC adhesion complex. Aim 3: Determine whether beta1 (VLA-4) and beta2 (LFA-1) integrins are functionally equivalent in T cell costimulation.