RECEPTORS FOR IMMUNOGLOBULIN G ON LEUKOCYTES

IgG受体（FcR）存在于白细胞效应子上， 非适应性防御系统对病原体，他们 作为细胞内和细胞外的连接结构 隔间 通过结合特定的免疫球蛋白或抗原- 抗体复合物，FcR允许靶向非免疫细胞 免疫反应的特定蛋白质的活性。 FcR 配体相互作用和几种淋巴因子都能间接调节 这些细胞在抵抗病原体方面的功能， IgG和其它分子受体的表面表达 (e.g.增长因素）。 我们的数据表明， 自然杀伤（NK）细胞的膜FcR（CD 16抗原）， 其特异性配体或单克隆抗CD 16抗体， 模拟配体最终导致其中一种或两种激活 和NK细胞的失活，如超微结构所证实的 变化，新的mRNA转录和FcR- 独立和非独立函数。 我们的假设是 NK细胞上的低亲和力FcR作为信号转导， 结构与其配体相互作用。 为了验证这个，我们 将：a）确定FcR-配体 相互作用将激活信号传递给细胞， 分子水平，B）分析CD 16分子作为配体的作用- 依赖性离子通道，c）剖析FcR- 配体相互作用诱导细胞毒性和 人NK细胞的增殖潜力。 定义统一或 FcR和FcR依赖性的行为的显著特征 非适应性防御系统的不同细胞的功能， 我们将比较NK细胞上FcR的功能特性， 与粒细胞上相似的FcR类型。 实验 也将进行以确定高亲和力FcR 单核细胞和白细胞介素激活的粒细胞，如CD 16 NK细胞和PMN上的分子。

Receptors for IgG (FcR) are present on leukocytes effector of non-adaptive systems of defense against pathogenes, and they function as linking structures between the intra- and extracellular compartments. By binding specific immunoglobulins or antigen- antibody complexes, FcR allow the targeting of non-immune cells activities by the specific proteins of the immune response. FcR- ligand interaction and several lymphokines both variably modulate the functions of these cells in resistance to pathogens, and the surface expression of receptors for IgG and for other molecules (e.g. growth factors). Our data indicate that the interaction of membrane FcR (CD16 antigen) of natural killer (NK) cells with their specific ligand or with monoclonal anti-CD16 antibodies that mimic the ligand eventually results in either or both activation and inactivation of NK cells, as evidentiated by ultrastructural changes, novel mRNA transcription and modulation of both FcR- dependent and -independent functions. Our working hypothesis is that the low affinity FcR on NK cells act as signal-transducing structures upon interaction with their ligands. To test this, we will: a) determine the mechanism(s) by which FcR-ligand interactions impart activation signals to the cells at the molecular level, b) analyze the role of CD16 molecule as ligand- dependent ion channel, c) dissect the mechanism by which FcR- ligand interactions induce modulation of cytotoxic and proliferative potential of human NK cells. To define unifying or distinctive features of behaviour of FcR and FcR-dependent functions of different cells of the non-adaptive system of defense, we will compare the functional properties of FcR on NK cells with those of a similar FcR type on granulocytes. Experiments will also be performed to determine whether the high affinity FcR on monocytes and cytokine-activated granulocytes, like the CD16 molecule on NK cells and PMN.