Human Natural Killer Cell Biology

描述（由申请人提供）：该计划采用广泛的方法来了解人类自然杀手（NK）细胞生物学。该计划各单位所代表的各种科学专业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传导的途径，并确定它们在NK细胞功能中的作用。Lanier将定义CDS在人类NK细胞中的作用，并描述新的NK细胞受体信号通路，重点是NK细胞的激活。Parham将描述影响受体表达的NK细胞受体多态性（包括蛋白质和启动子水平），并测试其功能效应。另一个单元将探索影响NK细胞受体功能的膜交通途径，并确定信号通路和受体多态性如何影响这些途径。这些单位将共同关注影响激活和抑制受体之间信号平衡的分子途径，这种平衡对NK细胞功能至关重要。该计划的第二个目标是建立NK细胞功能的分子机制的临床重要性。Nixon和Michaelsson将研究NK细胞在HIV感染过程中的作用。在疾病及其治疗过程中NK细胞亚群表达和受体使用的模式将被定义。该项目的首席研究员（Brodsky）在分析淋巴样细胞的膜交通途径方面具有专业知识。虽然对NK细胞是新的，但Brodsky的项目通过应用细胞生物学来定义与免疫学和遗传学有关的途径，为其他单位提供了一个重点。Parham和Lanier是NK细胞领域的专家，有着成功的合作历史。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染设备。总的来说，这个项目将把人类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.