Human Natural Killer Cell Biology

描述(由申请者提供)：该计划采取广泛的方法，以获得对人类自然杀手(NK)细胞生物学的了解。该计划各单位所代表的各种科学专门知识将集中在两个目标上。首先，这些单位之间的合作将阐明控制人类NK细胞受体表达和信号的途径，并确定它们在NK细胞功能中的作用。拉尼尔将定义CDS在人类NK细胞上的作用，并表征新的NK细胞受体信号通路，重点是NK细胞的激活。帕拉姆将描述影响受体表达的NK细胞受体多态(在蛋白质和启动子水平上)，并测试它们的功能效果。另一个单元将探索影响NK细胞受体功能的膜交通通路，并确定信号通路和受体多态如何影响这些通路。这些单位将共同关注影响来自激活和抑制受体的信号之间平衡的分子通路，这种平衡对NK细胞功能至关重要。该计划的第二个目标是确定NK细胞功能的分子机制的临床重要性。尼克松和迈克尔森将研究自然杀伤细胞在艾滋病毒感染过程中的作用。将确定在疾病及其治疗过程中NK细胞亚群的表达和受体使用的模式。该项目的首席研究员(Brodsky)在分析淋巴样细胞的膜运输途径方面拥有专业知识。虽然对NK细胞来说还是个新事物，但布罗斯基的计划通过应用细胞生物学来定义免疫学和遗传学所涉及的途径，为其他单位提供了一个重点。帕拉姆和拉尼尔是NK细胞领域的专家，有成功合作的历史。该计划的人员将定期会面，并将受益于专门用于显微镜和单克隆抗体生产的核心，以及研究人类NK细胞功能所需的共享转基因设备。总体而言，该计划将把对人类NK细胞的基本机制研究与这些细胞在HIV感染中的功能联系起来。

DESCRIPTION (provided by applicant): This program takes a broad approach to gain understanding of human natural killer (NK) cell biology. The varied scientific expertise represented by the units of the program will concentrate on two goals. Firstly, collaboration between the Units will elucidate pathways controlling human NK cell receptor expression and signaling and establish their role in NK cell function. Lanier will define CDS's role on human NK cells and characterize novel NK cell receptor signaling pathways, with emphasis on NK cell activation. Parham will characterize NK cell receptor polymorphisms that influence receptor expression (both at the protein and promoter level) and test their functional effects. Another unit will explore membrane traffic pathways that influence NK cell receptor function and determine how signaling pathways and receptor polymorphisms affect these pathways. Together the units will focus on molecular pathways that influence the balance between signals coming from activating and inhibitory receptors, a balance that is central to NK cell function. The program's second goal is to establish the clinical importance of molecular mechanisms of NK cell function. Nixon and Michaelsson will study the role of NK cells during HIV infection. Patterns of NK cell subset expression and receptor usage during the course of disease and its treatment will be defined. The program's principal investigator (Brodsky) has expertise in analyzing membrane traffic pathways in lymphoid cells. While new to NK cells, Brodsky's program provides a focus for the other units through the application of cell biology to define pathways implicated by the immunology and genetics. Parham and Lanier are experts in the NK cell field and have a history of successful collaboration. The program's personnel will meet regularly and will benefit from cores dedicated to microscopy and to monoclonal antibody production, as well as shared transfection equipment necessary for studying human NK cell function. Overall, this program will link basic mechanistic studies on human NK cells to the functions of these cells in HIV infection.