RECEPTORS FOR IMMUNOGLOBULIN G ON LEUKOCYTES

IgG的Fc部分的受体（Fc γ R）在大多数免疫球蛋白上表达。 造血细胞类型 通过结合抗原特异性免疫球蛋白， 它们提供了细胞内和细胞外 细胞之间的相互作用是必不可少的。 非适应性（先天）和适应性防御系统。 他们属于 与膜受体的异质性家族相关联， 抗体抗原复合物的细胞反应。 之多样 这些反应是结构异质性的结果， Fc γ R，与其胞质内结构域的差异有关， 在受体复合物或受体相关的存在下， 对受体表达和信号传导都很重要的分子 转导 我们已经证明，低亲和力的受体， 自然杀伤（NK）细胞和巨噬细胞（Fc γ RIIIA）上表达的IgG 一种跨膜糖蛋白，在配体结合后调节功能 这些细胞通过转导信号导致细胞活化。 其在多形核中性粒细胞（Fc γ RIIIB）上的对应物，a 糖硅磷脂酰肌醇连接的分子，缺乏这种 功能协调发展的 通过Fc γ RIII诱导的NK细胞活化主要依赖于 对激酶的诱导激活。 这个理论的工作假设是 建议是，不同的专门效应器功能介导的 不同的Fc γ R类型，这取决于诱导不同的 在相同或不同的细胞类型的生化事件， Fc γ R与其它蛋白质的相互作用在该功能中协同作用。 为了阐明不同类型的Fc γ R对NK细胞的作用， 细胞，骨髓单核细胞和淋巴细胞，我们建议：1）识别 这些分子在Fc γ RIII与NK细胞相互作用时被激活， 细胞与其配体，调节信号转导，和2）分析 不同Fc γ R的功能作用及其调节机制 B淋巴细胞和骨髓单核细胞上的类型。 我们特别 建议鉴定Fc γ RIII-配体激活的激酶 约束力 这些激酶的底物的作用， 磷酸酶，在控制Fc γ RIII介导的信号转导中 也将进行分析。 发生在 骨髓/单核细胞和B淋巴细胞 将研究不同Fc γ R之间的相互作用， 将对相同细胞类型进行解剖，以确定 由Fc γ RII在这些细胞上发挥作用。 这些研究预计将 导致识别的共同或独特的特点， FcgammaR的行为，以提供关于FcgammaR依赖性 造血细胞的功能，并提出理解的基础 先天免疫系统细胞功能的机制 防御是有规律的。

Receptors for the Fc portion of IgG (FcgammaR) are expressed on most hematopoietic cell types. By binding antigen specific immunoglobulins, they provide an important link between the intra and extracellular compartments and are essential for the interactions between cells of the non adaptive (innate) and the adaptive systems of defense. They belong to an heterogeneous family of membrane receptors and mediate a wide array of cellular responses to antibody antigen complexes. The diversity of these responses is the result of the structural heterogeneity of the FcgammaR, related to differences in their intracytoplasmic domains, and to the presence, within the receptor complex, or receptor associated molecules that are important both for receptor expression and signal transduction. We have demonstrated that the low affinity receptor for IgG expressed on Natural Killer (NK) cells and macrophages (FcgammaRIIIA) transmembrane glycoprotein that, upon ligand binding, regulates functions of these cells by transducing signals that result in cell activation. Its counterpart on polymorphonuclear neutrophils (FcgammaRIIIB), a glycosilphosphatidylinositol linked molecule, is devoid of such functions. NK cell activation induced via FcgammaRIII primarily depends on induced activation of kinases. The working hypothesis of this proposal is that distinct specialized effector functions are mediated by different FcgammaR types, that depend on induction of distinct biochemical events in the same or different cell types, and that interactions of FcgammaR with other proteins cooperate in this function. In order to elucidate the role of the different types of FcgammaR on NK cells, myelomonocytic cells, and lymphocytes, we propose: 1) to identify those molecules that, activated upon interaction of FcgammaRIII on NK cells with its ligands, regulate signal transduction, and 2) to analyze functional role, an the mechanisms regulating them, of distinct FcgammaR types on B lymphocytes and myelomonocytic cells. Specifically, we propose to identify the kinases activated upon FcgammaRIII-ligand binding. The role of the substrates for these kinases, and of phosphatases, in controlling FcGgammaRIII-mediated signal transduction will also be analyzed. The molecular events occurring in myeloid/monocytic cells and B lymphocytes upon immune complexes binding will be studied and the interactions between different FcgammaR expressed on the same cell types will be dissected, to determine the relative role played by FcgammaRII on these cells. These studies are expected to result in the identification of common or distinctive features of behavior of FcgammaR, to provide information on FcgammaR-dependent functions on hematopoietic cells, and to pose the basis for understanding the mechanisms by which functions of cells of the innate system of defense are regulated.