STRUCTURE AND FUNCTION OF CD32 ON NK CELLS

对自然的生物学和活体意义的认识 杀手细胞是许多研究人员的主要关注焦点 匹兹堡癌症研究所(PCI)的免疫学项目。The Rapid 将实验室结果转化为临床方案，特别是 在生物反应调节剂和免疫疗法领域 特别感兴趣。这包括方法，如使用 过继细胞免疫疗法、细胞因子疗法及其他 大剂量静脉注射免疫球蛋白等天然生物制品 (IVIG)治疗。关于调查潜在的 IVIG治疗方面，已经有了长期的研究合作 PCI和布加勒斯特免疫学中心(BCI)的调查人员 主要研究NK细胞表面Fc受体(FCR)的表达和功能 免疫球蛋白结合对NK细胞生理功能的影响。由于这些原因， 互动，我们最近首次演示了 人NK细胞表面Fc/γ/RII(CD32)的表达这些数据是 特别有趣的是，因为人们普遍认为NK细胞表达 只有Fc/Gamma/RIII(CD16)，低亲和力的免疫球蛋白受体。AS 这些Fc/γ/R的表达及其与免疫球蛋白的相互作用是 对于评价IVIG治疗的意义，重要的是 CD32的天然NK细胞相关亚型(S)有待阐明。基座 根据我们的发现，我们建议将生物化学、分子 和NK细胞相关CD32的功能特征，并与 具有已知形式的CD32和CD16的特征。我们的具体目标 包括： 1.NK细胞相关Fc/γ/RII的生化特性 (CD32)和单个或多个表达的确定 NK细胞对该受体亚型的研究。 2.编码NK细胞特异性c DNA(S)的分子鉴定 Fc/Gamma/RII(CD32)相关亚型(S)。 3.NK细胞配体结合特性的测定 相关的Fc/Gamma/RII亚型(S)。 4.NK细胞相关Fc/γ/RII的功能分析。 这些研究的结果将从以下两方面具有重要意义 提高对森林资源的性质和分布的认识的观点 CD32，某些功能的激活，如细胞毒性和 自然杀伤细胞产生细胞因子及静脉注射免疫球蛋白的潜在作用 治疗对NK细胞功能的影响。

An understanding of the biology and in vivo significance of natural killer cells is a primary focus of many of the investigators in the Immunology Program of the Pittsburgh Cancer Institute (PCI). The rapid translation of laboratory findings into clinical protocols, especially in the area of Biologic Response Modifiers and immunotherapy is of particular interest. This includes approaches such as the use of adoptive cellular immunotherapy, cytokine therapy and the use of other natural biological products such as high dose intravenous immunoglobulin (IVIG) therapy. In regards to the investigation of the potential for IVIG therapy, there has been a long term, research collaboration among investigators at the PCI and at the Bucharest Center for Immunology (BCI) focused on the expression and function of Fc receptors (FcR) on NK cells and effects of IgG binding on NK cell physiology. As a result of these interactions, we have recently demonstrated for the first time the expression of Fc/gamma/RII (CD32) on some human NK cells. These data are of particular interest, as it is commonly accepted that NK cells express only Fc/gamma/RIII (CD16)), the low affinity receptor for IgG. As expression of these Fc/gamma/R, and their interactions with IgG is of significance for the evaluation of IVIG therapy, it is of importance that the nature NK cell-associated isoform(s) of CD32 to be elucidated. Based upon our findings, we propose to characterize the biochemical, molecular and functional features of NK cell-associated CD32, and compare those features with the known forms of CD32 and with CD16. Our specific aims include: 1. Biochemical characterization of NK cell-associated Fc/gamma/RII (CD32) and the determination of the expression of a single or multiple isoforms of this receptor by NK cells. 2. Molecular characterization of specific cDNA(s) encoding the NK cell- associated isoform(s) of Fc/gammam/RII (CD32). 3. Determination of the ligand binding characteristics of the NK cell associated Fc/gamma/RII isoform(s). 4. Functional analyses of NK cell-associated Fc/gamma/RII. The results of these studies will be of significance both from the standpoint of increased understanding of the nature and distribution of CD32, the activation of certain functions such as cytotoxicity and cytokine production by NK cells, and the potential effects of IVIG therapy on NK cell function.