MEMBRANE ANCHORING AND FUNCTION OF CD16

关于Fc受体的结构和功能的知识是 了解免疫系统防御的基础知识。在……里面 人、三种类型免疫球蛋白Fc的结构和结合特性 受体(Fc-γ-Rs)已被描述。这些Fc-Gamma-yRIII (CD16)已被证明具有重要的生理意义。CD16，是一种 50-70kD的糖蛋白，表达在中性粒细胞上，自然杀伤 (NK)细胞、嗜酸性粒细胞和组织巨噬细胞。活体研究使用 CD16单抗已证明CD16在免疫应答中起重要作用。 清除循环中的免疫复合体。CD16有两个截然不同的 膜锚.中性粒细胞中的磷脂酰肌醇多聚糖(猪)和 NK细胞中的多肽。CD16在PNH中表达不足 获得性造血干细胞疾病对血管内皮生长因子表达的影响 猪锚定蛋白。建议的研究使用CD16阴性的PNH 检测CD16表达缺陷是否会导致中性粒细胞 中性粒细胞功能异常与Fc依赖功能的比较 正常和PNH中性粒细胞重组CD16前后 表情。多肽锚定CD16的功能研究 在相同的条件下，NK细胞的表达也将被比较。 这些研究将描绘CD16缺乏对 中性粒细胞及膜锚定对CD16功能的影响。 这一建议还着眼于建立稳定的转染体。 表达/分泌各种形式的CD16。因为没有细胞系 CD16的表达是可用的，稳定的转染体将是一个极好的 进一步研究结构/功能的工具。CD16的各种形式 将从这些稳定的转染体的大规模培养中提纯 以及生化和功能表征。从功能上讲 表征的纯化分子可以用来定义这些分子的作用 细胞功能中的受体。在未来，纯化的CD16可能会 直接用于治疗慢性免疫等疾病 血小板减少性紫癜与预防Fc介导的HIV等病毒 感染。或者，完全了解其结构和 功能可能有助于设计治疗该病的治疗剂 这些疾病。

The knowledge of the structure and function of Fc receptors is fundamental in understanding the defense of the immune system. In humans, the structure and binding properties of three types of IgG Fc receptors (Fc-gamma-Rs) have been described. Of these Fc-gamma-yRIII (CD16) has demonstrated to be physiologically important. CD16, is a glycoprotein of 50-70 kD and is expressed on neutrophils, natural killer (NK) cells, eosinophils and tissue macrophages. In vivo studies using CD16 monoclonal antibodies have demonstrated that CD16 plays a major role In clearing immune complexes from the circulation. CD16 has two distinct membrane anchors; phosphatidylinositol glycan (PIG) in neutrophils and a polypeptide in NK cells. CD16 is deficiently expressed in PNH, an acquired hematopoietic stem cell disease which affect the expression of PIG-anchored proteins. The proposed research uses CD16 negative PNH neutrophils to test whether the defect in CD16 expression leads to abnormal neutrophil functions by comparing the Fc dependent functions of normal and PNH neutrophils before and after reconstituting CD16 expression. The functional ability of polypeptide-anchored CD16 expression on NK cells will also be compared under the same conditions. These studies will delineate the consequences of CD16 deficiency on neutrophils and the influence of membrane anchor on the function of CD16. This proposal is also focused on establishing stable transfectants expressing/secreting various forms of CD16. Since no cell lines that express CD16 are available, the stable transfectants will be an excellent tool for further structure/function studies. The various forms of CD16 will be purified from large scale cultures of these stable transfectants and biochemically and functionally characterized. The functionally characterized purified molecule can be used to define the role of these receptors in cellular functions. In the future, a purified CD16 may directly be used therapeutically to treat diseases such as chronic immune thrombocytopenic purpura and prevent Fc mediated HIV and other viral infections. Alternatively, complete knowledge of its structure and function may be useful in designing therapeutic agent for treatment of these diseases.