STRUCTURE AND FUNCTION OF CD32 ON NK CELLS

NK 细胞上 CD32 的结构和功能

• 批准号: 2292120
• 负责人: WILLIAM H CHAMBERS
• 金额: $ 2.34万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2292120
• 关键词: antibody receptor; complementary DNA; cytokine; cytotoxicity; enzyme linked immunosorbent assay; human tissue; monoclonal antibody; natural killer cells; nucleic acid sequence; protein isoforms; protein structure function; western blottings

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.

了解自然界的生物学和体内意义， 杀伤细胞是许多研究人员的主要焦点， 匹兹堡癌症研究所（PCI）的免疫学项目。 快速 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治疗领域， 特别的兴趣。 这包括使用 过继性细胞免疫疗法、细胞因子疗法和其它免疫疗法的应用 大剂量静脉注射免疫球蛋白等天然生物制品 （IVIG）疗法。 关于调查潜在的 IVIG治疗，有一个长期的研究合作， PCI和布加勒斯特免疫学中心（BCI）的研究人员 主要关注NK细胞上Fc受体（FcR）的表达和功能 以及IgG结合对NK细胞生理学的影响。 由于这些 最近，我们首次证明了 Fc/γ/RII（CD 32）在一些人NK细胞上的表达。 这些数据 特别令人感兴趣的是，因为通常认为NK细胞表达 仅Fc/γ/RIII（CD 16）），IgG的低亲和力受体。 作为 这些Fc/γ/R的表达，以及它们与IgG的相互作用， 重要的是， 待阐明的天然NK细胞相关的CD 32同种型。 基于 根据我们的研究结果，我们提出了生物化学，分子， 和NK细胞相关CD 32的功能特征，并比较它们 与已知形式的CD 32和CD 16的特征。 我们的具体目标 包括以下步骤： 1. NK细胞相关Fc/γ/RII的生化表征 （CD 32）和确定单个或多个CD 32的表达。 这种受体的亚型通过NK细胞。 2. 编码NK细胞的特定cDNA的分子表征- Fc/γ/RII（CD 32）的相关同种型。 3. NK细胞配体结合特性的测定 相关的Fc/γ/RII同种型。 4. NK细胞相关Fc/γ/RII的功能分析。 这些研究的结果将具有重要意义， 的性质和分布的认识， CD 32，某些功能如细胞毒性的激活， NK细胞产生的细胞因子，以及IVIG的潜在作用 NK细胞功能的治疗。