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

人T淋巴细胞CD 2（T11）分子在淋巴细胞中早期表达。 胸腺个体发育和大多数人T细胞。 几行 有证据表明，CD 2是一种参与T细胞增殖的受体， 粘附、活化和分化。 CD 2的配体具有 淋巴细胞功能相关抗原-3（LFA-3）。 拟议的项目侧重于CD 2的功能作用， T细胞活化及其与其配体LFA-3的相互作用。 的 本项目的目标是了解监管作用的 CD 2分子在T细胞活化中的作用及其结构特征 CD 2对LFA-3结合和信号传导的要求 转导 缺乏LFA-3结合位点的突变CD 2分子 并且活化相关的CD 2表位将被产生、表达 在抗原特异性T细胞杂交瘤中，并进行分析。 删除 将产生并分析CD 2胞质结构域的突变体， 以帮助定义通过 CD2。 野生型和突变的CD 2分子将用于 分析信号转导机制。 可溶性LFA-3将 在有效的表达系统中产生，并用于表征， CDLFA 3与CD 2的结合。 基于氨基的合成肽 将分析CD 2和LFA-3的酸性序列，以确定更多 准确地说是结合位点。 这种方法最终可能导致 CD 2/LFA的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，CD 2/LFA-3 相互作用可以增强抗原特异性应答。 LFA-3 与CD 2结合的配体可增强或调节T细胞活化。 CD 2/LFA-3最低要求的定义 受体-配体相互作用和信号传导可能有助于我们的研究。 了解免疫调节和调制 反应 理解这种相互作用可能最终导致 增强T细胞应答的新免疫学方法 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.