Defining the functional role of CD56 on human natural killer cells

定义 CD56 对人类自然杀伤细胞的功能作用

基本信息

批准号：
10735537
负责人：
Emily Margaret Mace
金额：
$ 33.88万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10735537
关键词：
Actin-Binding Protein Actins Activated Natural Killer Cell Binding Biochemical Biological Process Biology CD44 Antigens Cell Adhesion Cell Communication Cell Line Cell Surface Receptors Cell membrane Cell physiology Cells Cellular biology Complex Cytoskeleton Data Diffusion Disease Electrostatics Extracellular Domain Genetic Glycocalyx Glycoproteins Health Human Immune Immunoprecipitation Immunotherapy Integrins Label Link Literature Lymphocyte Malignant Neoplasms Mass Spectrum Analysis Mediating Membrane Membrane Microdomains Microscopy Modification Molecular Mus NCAM1 gene Natural Killer Cells Neural Cell Adhesion Molecules Neurons Neurophysiology - biologic function Phenotype Phosphotransferases Physiological Play Polymers Polysialic Acid Population Property Protein Isoforms Proteins Regulation Role Signal Transduction Signaling Protein Site Spectrin Testing Translating Virus Diseases Work biomarker identification cancer immunotherapeutics cell fixing cell killing cell motility cell type cytotoxic cytotoxicity density fighting insight member migration polymerization prevent receptor recruit scaffold single molecule spectrin-binding proteins tool tumor

项目摘要

Project summary Human natural killer (NK) cells are critical for control of viral infection and their importance for tumor surveillance is underscored by their emerging use as a cancer immunotherapeutic tool. Understanding unique aspects of human NK cells that are not uncovered by the biology of murine NK cells is critical to advancing our use of NK cells in immunotherapy. CD56, which is the glycoprotein neural cell adhesion molecule (NCAM), is ubiquitously expressed on human, but not mouse, NK cells. In part because of its uniquely human expression, the molecular function of CD56/NCAM has not elucidated on immune cells. Our preliminary data demonstrates that CD56/NCAM plays a functional role on human NK cells and indicates key aspects of unique CD56/NCAM biology that dictate its function. To delineate this function, we will closely examine three aspects of CD56/NCAM function in three independent aims. Aim 1 will determine the functional effect of the addition of polysialic acid to CD56/NCAM and the role that the steric properties of polysialic acid have on the membrane diffusion of CD56/NCAM and other NK cell activating receptors and integrins. Aim 2 will define the linkage between CD56/NCAM and the NK cell cytoskeleton, including delineating the link between CD56 and actin. Aim 3 will identify intracellular binding partners of CD56/NCAM and determine the role that lipid raft recruitment plays in its signaling and function. Together, these aims will delineate the function of this universally expressed and but poorly understood receptor on human NK cells. It will also provide critical insight into the functional role that CD56/NCAM, and glycoproteins in general, play in dictating critical NK cell functions including cell migration and target cell killing.

项目概要人类自然杀伤 (NK) 细胞对于控制病毒感染及其对肿瘤的重要性至关重要它们作为癌症免疫治疗工具的新兴用途强调了监测。理解独特鼠 NK 细胞生物学未发现的人类 NK 细胞的某些方面对于推进我们的研究至关重要 NK 细胞在免疫治疗中的应用。 CD56 是糖蛋白神经细胞粘附分子 (NCAM)，普遍表达于人类 NK 细胞，但不表达于小鼠 NK 细胞。部分原因是其独特的人类表达方式， CD56/NCAM对免疫细胞的分子功能尚未阐明。我们的初步数据表明 CD56/NCAM 对人类 NK 细胞发挥功能性作用，并表明独特 CD56/NCAM 的关键方面决定其功能的生物学。为了描述这一功能，我们将仔细研究以下三个方面： CD56/NCAM在三个独立的目标中发挥作用。目标 1 将确定添加的功能效果聚唾液酸对 CD56/NCAM 的影响以及聚唾液酸的空间特性对膜的作用 CD56/NCAM 和其他 NK 细胞激活受体和整合素的扩散。目标 2 将定义联系 CD56/NCAM 和 NK 细胞细胞骨架之间的关系，包括描绘 CD56 和肌动蛋白之间的联系。目标 3 将鉴定 CD56/NCAM 的细胞内结合伴侣并确定脂筏的作用招募发挥其信号传导和功能。这些目标将共同描述该机构的职能人类 NK 细胞上普遍表达但了解甚少的受体。它还将提供重要的见解 CD56/NCAM 和一般糖蛋白在决定关键 NK 细胞中发挥的功能作用功能包括细胞迁移和靶细胞杀伤。