SPECIFICITY/DISTRIBUTION/FUNCTION/GAMMA:DELTA T CELLS

特异性/分布/功能/伽玛：DELTA T 细胞

• 批准号: 3142139
• 负责人: CHARLES A JANEWAY
• 金额: $ 18.55万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3142139
• 关键词: CD3 molecule; T cell receptor; T lymphocyte; antireceptor antibody; clone cells; epithelium; gene expression; immunofluorescence technique; in situ hybridization; laboratory mouse; leukocyte activation /transformation; lymphokines; major histocompatibility complex; monoclonal antibody; receptor expression

The overall goal of this project is to determine the specificity, distribution, and function of Tcells bearing the newly described T cell receptor comprising the gamma:delta heterodimer associated with CD3, which we refer to as TCR1. Our working hypothesis is that TCR1 is specific for class I MHC gene products distinct from conventional class I genes in the murine MHC (class IB), and that their principal role is surveillance of the integrity of epithelial cell membranes. To test this hypothesis, the following experiments will be carried out: Intraepithelial lymphocytes will be isolated and tested for expression of mRNA encoding TCR genes, and for surface expression of TCR protein by precipitation with anti-CD3 or anti-TCR antibodies, and by immunofluorescence for cell surface phenotype and receptor expression where reagents are available. Isolated TCR1-bearing T cells will be stimulated with antigen or with anti-receptor antibody, propagated in IL-2, and cloned and/or hybridized to TCR-negative T lymphoma cells to provide a stable source of TCR1 bearing T cells. The function of freshly isolated TCR1 bearing T cells or of cloned lines or hybrids will be studied using anti-CD3 antibody as a mock ligand. The activation requirements of resting as well as cloned TCR1 bearing T cells will be studied, as will the production of lymphokines and the response to lymphokines of these cells. Finally, these cells will be used to determine the ligand specificity of TCR1 bearing T cells isolated from epithelia, by stimulation with L cells transfected with various MHC genes. If such a gene does activate a TCR1 bearing cell, its expression in normal, infected and transformed cells of that tissue will be examined to determine if differential expression of that gene could account for TCR1-mediated epithelial surveillance.

本项目的总体目标是确定特异性， 携带新描述的T细胞的T细胞的分布和功能 包含与CD 3相关的γ：δ异二聚体的受体， 我们称之为TCR 1。 我们的工作假设是TCR 1是 特异于不同于常规I类MHC基因产物的I类MHC基因产物 基因在鼠MHC（IB类），其主要作用是 监测上皮细胞膜的完整性。 为了验证这一 假设，将进行以下实验： 将分离上皮内淋巴细胞并检测其表达， 用于TCR蛋白的表面表达， 用抗CD 3或抗TCR抗体沉淀，以及 细胞表面表型和受体表达免疫荧光 在试剂可用的地方。 分离的携带TCR 1的T细胞将用抗原刺激或用 抗受体抗体，在IL-2中增殖，并克隆和/或杂交 TCR阴性T淋巴瘤细胞，以提供稳定的TCR 1 携带T细胞 新鲜分离的携带TCR 1的T细胞或克隆系的功能 或将使用抗CD 3抗体作为模拟配体来研究杂交体。 的 静息以及克隆的携带TCR 1的T细胞的活化要求 将进行研究，淋巴因子的产生和反应也将如此。 这些细胞的淋巴因子。 最后，这些细胞将被用于确定的配体特异性 通过用L细胞刺激从上皮分离的携带TCR 1的T细胞 用各种MHC基因转染。 如果这样的基因确实激活了TCR 1 其在正常、感染和转化细胞中的表达， 该组织将被检查以确定是否差异表达 该基因可以解释TCR 1介导的上皮监视。