INTERACTION OF CD-2 WITH LFA-3 IN T CELL ACTIVATION

人T淋巴细胞CD2(Tll)分子在早期表达 胸腺个体发育和大多数人类T细胞。几行 有证据表明CD2是T细胞中的一种受体 黏附、激活和分化。CD2的一个配体已经 已发现为淋巴细胞功能相关抗原-3(LFA-3)。 拟议的项目重点放在CD2在 T细胞活化及其与其配体LFA-3的相互作用。这个 本项目的目标是了解 CD2分子在T细胞活化中的作用及结构描绘 CD2对LFA-3结合和信号的要求 转导。缺乏LFA-3结合位点的突变CD2分子 并将产生与激活相关的CD2表位，表达 在抗原特异性T细胞杂交瘤中，并进行了分析。删除 将产生和分析CD2细胞质结构域的突变体 帮助定义信令通过的结构要求 CD2。野生型和突变的CD2分子将用于 分析信号转导机制。可溶性LFA-3将 在高效的表达系统中产生，并用于鉴定 将LFA3绑定到CD2。基于氨基的合成肽 CD2和LFA-3的酸序列稍后将被分析以定义更多 准确地说是结合部位。这种方法最终可能会导致 CD2/LFA小分子激动剂或抑制剂的设计 3互动。越来越多的证据表明CD2/LFA-3 相互作用可以增强抗原特异性反应。LFA-3 与CD2的配体结合可以增强或调节T细胞的激活。 CD2/LFA-3最低要求的定义 受体-配体相互作用和信号转导可能有助于我们的 对免疫的调节和调节的认识 回应。理解这种互动最终可能会导致 增强T细胞应答的新免疫治疗方法 到弱病毒或肿瘤特异性抗原。

The human T lymphocyte CD2 (Tll) molecule is expressed early in thymic ontogeny and on most human T cells. Several lines of evidence suggest that CD2 is a receptor involved in T cell adhesion, activation, and differentiation. A ligand for CD2 has been found to be lymphocyte-function associated antigen-3 (LFA-3). The proposed project focuses on the functional role of CD2 during T cell activation and its interaction with its ligand, LFA-3. The goal of this project is to understand the regulatory role of the CD2 molecule in T cell activation and to delineate the structural requirements of CD2 for both LFA-3 binding and for signal transduction. Mutated CD2 molecules which lack LFA-3 binding sites and activation-related CD2 epitopes will be generated, expressed in an antigen-specific T cell hybridoma, and analyzed. Deletion mutants of the CD2 cytoplasmic domain will be generated and analy to help to define the structural requirements for signaling through CD2. The wild type and mutated CD2 molecules will be used to analyze the mechanisms of signal transduction. Soluble LFA-3 will be produced in an efficient expression system, and used to charac- terize LFA3 binding to CD2. Synthetic peptides based on the amino acid sequence of CD2 and, later, LFA-3 will be analy to define more precisely the binding site. This approach may ultimately lead to the design of small molecule agonists or inhibitors of the CD2/LFA- 3 interaction. There is accumulating evidence that the CD2/LFA-3 interaction can augment the antigen-specific response. LFA-3 ligand binding to CD2 may enhance or modulate T cell activation. The definition of the minimum requirements for the CD2/LFA-3 receptor-ligand interaction and for signaling may contribute to our understanding of the regulation and modulation of the immune response. Understanding this interaction may ultimately lead to novel immunotherapeutic approaches to enhance the T cell response to weak viral or tumor-specific antigens.