DIFFERENTIATION ANTIGENS ON HUMAN T CELL SUBCLASSES

人类 T 细胞亚类的分化抗原

• 批准号: 3125953
• 负责人: Leonard Chess
• 金额: $ 25.4万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3125953
• 关键词: B lymphocyte; CD antigens; CD4 molecule; CD8 molecule; MHC class II antigen; Retroviridae; T lymphocyte; antibody dependent killer cell; antigen presenting cell; cell cell interaction; cell differentiation; cell population study; cellular immunity; chemical structure function; clone cells; genetic library; glycoproteins; helper T lymphocyte; human subject; immunogenetics; laboratory mouse; macrophage; mixed lymphocyte reaction test; monoclonal antibody; nucleic acid probes; nucleic acid sequence; radiotracer; receptor binding; recombinant DNA; suppressor T lymphocyte; surface antigens; tissue /cell culture; transfection; transposon /insertion element; western blottings

The human immune response is generated and regulated by a complex set of cellular interactions between subsets of T cells, B cells and antigen-presenting macrophages. The molecules which govern these interactions are surface membrane glycoproteins which become expressed during differentiation. Many of these molecules define unique subsets of cells and are also intimately involved in the function of the cells they define. During the last several years, our laboratory has been particularly concerned with the CD4 and CD8 molecules which are simultaneously expressed on the majority of thymocytes, but during terminal differentiation become expressed on the surface of the mutually exclusive subsets of T cells. Mounting evidence suggests that these molecules have dual functions. First, they are thought to be receptor structures for conserved regions of MHC molecules (CD4 recognizing class II and CD8 recognizing class I MHC). Second, they are involved in transmitting regulatory signals to T cells during antigen activation. In order to more precisely define the immunobiology of these molecules, we have isolated and sequenced the genes and cDNA's encoding these molecules. A major thrust of this renewal proposal will be to continue to employ recombinant DNA technology to create mutant CD4 and CD8 molecules and, following gene transfer to relevant cells and clones, define the structure function relationships of these molecules. In addition, we will extend these studies to other known functionally interesting differentiation antigens on immunocompetent cells, including CD5 which is expressed on T cells and a subset of B cells. Finally, we will employ the monoclonal antibody and gene isolation technologies which have been used successful to date in the analysis of DC 4 and CD8 in order to define new cell surface molecules important in the control of human T cell functions. Because T cells are known to be intimately involved in the immunopathology of most immunologic diseases of man, including AIDS, we believe our studies will contribute basic data that my be essential to further understanding of these diseases.

人体免疫反应是由一种复杂的物质产生和调节的 T 细胞、B 细胞亚群之间的一组细胞相互作用 和抗原呈递巨噬细胞。 控制的分子 这些相互作用是表面膜糖蛋白，它们变成 在分化过程中表达。 许多这些分子定义 独特的细胞亚群，也密切参与 他们定义的细胞的功能。 在过去的几年里， 我们的实验室特别关注CD4和CD8 同时在大多数细胞上表达的分子 胸腺细胞，但在终末分化期间表达 位于相互排斥的 T 细胞亚群的表面。 越来越多的证据表明这些分子具有双重作用 功能。 首先，它们被认为是受体结构 MHC 分子的保守区域（CD4 识别 II 类和 CD8 识别 I 类 MHC）。 其次，他们参与 在抗原过程中向 T 细胞传递调节信号 激活。 为了更准确地定义免疫生物学 对于这些分子，我们分离并测序了基因 编码这些分子的cDNA。 此次更新的一大亮点 建议继续采用重组 DNA 技术 创建突变型 CD4 和 CD8 分子，并在基因转移后 对相关细胞和克隆，定义结构函数 这些分子的关系。 此外，我们还将延长 这些研究对其他已知的功能有趣 免疫活性细胞上的分化抗原，包括 CD5 它在 T 细胞和 B 细胞子集上表达。 最后， 我们将采用单克隆抗体和基因分离 迄今为止已成功使用的技术 分析 DC 4 和 CD8 以定义新的细胞表面 控制人类 T 细胞功能的重要分子。 因为已知 T 细胞密切参与 大多数人类免疫疾病的免疫病理学，包括 艾滋病，我们相信我们的研究将提供我所需要的基本数据 对于进一步了解这些疾病至关重要。