KILLER CELL SURFACE ANTIGENS--BIOCHEMISTRY AND FUNCTION

自然杀伤(NK)细胞、细胞毒性T淋巴细胞(CTL)和 单核巨噬细胞(MP)代表三种主要的吞噬系统 宿主对肿瘤的防御。我们的实验室积极参与 在对细胞表面事件的分子解剖中， 这些细胞介导的细胞毒性反应，通过使用 作为结构和功能的探针的单抗。在这 项目，我们建议继续我们的研究，以考察 淋巴细胞功能相关抗原-1(LFA-1) 细胞毒细胞表面糖蛋白的异二聚体家族， 特别强调了NK系统和与之密切相关的 效应细胞，淋巴因子(IL-2)激活的杀伤细胞。 我们的实验室目前正在探索以下假设 细胞毒系统：(1)LFA-1家族的细胞表面密度 成员在细胞介导的细胞毒作用的表达中起重要作用 在这些系统中；(2)LFA-1从属于非粘着相关 在NK系统中发挥作用(S)，可能起到了后期作用 在细胞溶解机制中或在更全球性的调控中 细胞过程(例如，跨膜信号事件)；和(3) IL-2在调节细胞溶解活性中的一个重要作用 是通过增强LFA-1的表达，目前尚不清楚 机械装置。在这项竞争性续展申请中，我们 提出一系列旨在进一步测试这些结论的实验 通过详细研究假设的结构、功能、 这一重要表面家族的表达和生物合成 分子，以及试图分离和鉴定 NK系统中LFA-1的潜在靶细胞配体。在苏中 这样做，我们将继续追求更好的长期目标 在分子水平上理解细胞介导的宿主防御 对抗肿瘤。

Natural killer (NK) cells, cytotoxic T-lymphocytes (CTL's), and mononuclear phagocytes (MP) represent three major systems of host defense against tumors. Our laboratory is actively involved in the molecular dissection of cell-surface events important in the cytotoxic response mediated by these cells, through the use of monoclonal antibodies as probes of structure and function. In this project, we propose to continue our studies examining the role of the Lymphocyte Function-Associated Antigen-One (LFA-1) heterodimeric family of surface glycoproteins on cytotoxic cells, with special emphasis on the NK system and a closely-related effector cell, Lymphokine (IL-2)-Activated Killer Cells. Our laboratory is currently exploring the following hypotheses in cytotoxic systems: (1) that cell surface density of LFA-1 family members is important in expression of cell-mediated cytotoxicity in these systems; (2) that LFA-1 subserves non-adherence related function(s) in the NK system, possibly playing a role in a late step in the cytolytic mechanism or in more global regulation of cellular processes (e.g., transmembrane signalling events); and (3) that one important effect of IL-2 in modulating cytolytic activity is in enhancing expression of LFA-1, through as yet unknown mechanisms. In this Competing Continuation Application, we propose a series of experiments designed to further test these hypotheses through detailed study of the structure, function, expression, and biosynthesis of this important family of surface molecules, as well as proposals to attempt to isolate and identify the putative target cell ligand for LFA-1 in the NK system. In so doing, we will continue to pursue our long-term goal of better understanding, at the molecular level, cell-mediated host defense against tumors.