CELL SURFACE RECEPTORS ON CYTOTOXIC T CELLS

细胞毒性 T 细胞上的细胞表面受体

• 批准号: 3125996
• 负责人: CORNELIS P TERHORST
• 金额: $ 12.17万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3125996
• 关键词: T lymphocyte; affinity chromatography; antibody titering; cellular immunity; cytotoxicity; gel electrophoresis; human tissue; hybridomas; immunoregulation; liposomes; membrane activity; mixed lymphocyte reaction test; monoclonal antibody; radioimmunoassay; radiotracer; tissue /cell culture

The cytotoxic thymus derived lymphocyte (CTL) is a critical element in the effector phase of the immune response. It plays a central role in the destruction of virus-infected cells and in the rejection of foreign tissue grafts or tumors. Moreover, CTL's might also be involved in the pathogenesis of some autoimmune diseases. The main objective of this proposal is to study the target antigen recognition and the initial phase of signal transduction by T cell receptors. The intention of the proposed studies is to unravel the complexity of the T cell receptor/T3 complex on the surface of CTL, its biosynthesis and the possible molecular mechanisms of transmembrane signalling after ligand/receptor interaction has been established. In addition to a description of human T cell receptors specific for HLA-A2 and -B7 antigens, T cell receptor function of murine CTL will be studied. This system offers a number of unique advantages: 1) availability of well defined human and murine cytotoxic T cell clones and target cells. 2) assays by which receptor/antigen interactions can be studied are used routinely. 3) considerable information about the protein structure of the T cell receptor/T3 complex on human and murine T cells has been collected. 4) expertise in recombinant DNA technology has been introduced in our laboratory. The specific aims of the proposed project include: a) the study of the B and a-chains of the T cell receptor on the surface of human CTL's, b) the study of the role of the components of the T cell receptor/T3 complex in the early stages of cytolysis, c) investigation of the role of a2-microglobulin and the acessory structures T8 (Lyt2) and LFA-1 in recognition of class I MHC antigens by CTL, d) a detailed description of the components of the human and murine T cell receptor/T3 complex and its biosynthesis and, e) examination of the mode of signal transduction by the T cell receptor/T3 complex.

细胞毒性胸腺源性淋巴细胞（CTL）是免疫应答中的关键因素。 免疫反应的效应阶段。 它发挥着核心作用， 病毒感染细胞的破坏和外来组织的排斥 移植物或肿瘤。 此外，CTL也可能参与 某些自身免疫性疾病的发病机制。 本提案的主要目的是研究靶抗原 T细胞的识别和信号转导的初始阶段 受体。 拟议的研究的目的是解开 CTL表面上的T细胞受体/T3复合物的复杂性，其 生物合成和跨膜的可能分子机制 配体/受体相互作用后的信号传导已经建立。 在 除了对HLA-A2特异性的人T细胞受体的描述外， -B7抗原，研究小鼠CTL的T细胞受体功能。 该系统具有许多独特的优点： 1)明确定义的人和鼠细胞毒性T细胞克隆的可用性 和靶细胞。 2)通过该测定，可以测定受体/抗原相互作用， 研究是常规使用的。 3)关于蛋白质的大量信息 人和鼠T细胞上的T细胞受体/T3复合物的结构 被收集。 4)重组DNA技术的专业知识 在我们的实验室里。 拟议项目的具体目标包括： a）研究了人T细胞表面上T细胞受体的B链和a链， 人CTL，B）T细胞组分作用的研究 受体/T3复合物在细胞溶解的早期阶段，c）研究 α 2-微球蛋白和辅助结构T8（Lyt 2）的作用， LFA-1在CTL识别I类MHC抗原中的作用，d）详细的 人和鼠T细胞受体/T3组分的描述 复合物及其生物合成，以及，e）检查信号模式 通过T细胞受体/T3复合物的转导。