LIGANDS AND ACCESSORY FACTORS IN CD4+ T CELL PRIMING

CD4 T 细胞启动中的配体和辅助因子

• 批准号: 3140786
• 负责人: CHARLES A JANEWAY
• 金额: $ 16.19万
• 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: 1989-01-01 至 1993-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3140786
• 关键词: CD4 molecule; T cell receptor; T lymphocyte; antiAIDS agent; antigen presenting cell; antireceptor antibody; cell differentiation; hamsters; human immunodeficiency virus 1; interleukin 1; interleukin 2; laboratory mouse; laboratory rat; leukocyte activation /transformation; ligands; membrane proteins; monoclonal antibody; receptor coupling; receptor expression; tissue /cell culture

The most critical event in the induction of most-immune responses is the activation of a resting CD4+ T cell by antigen. This step in the immune response appears to require not only the presentation of sufficient ligand for the T cell receptor but accessory signals as well. This step leads to the generation of both memory and effector T cells. This step in immune responses is very difficult to analyze in detail, as it has not been mimicked effectively in vitro, and is usually studied by in vivo priming with antigen. The goal of the present studies is to use anti-T cell receptor antibody as a substitute for antigen, and to characterize priming of T cells using a variety of detection systems, some of which may not require T cell proliferation. Four different types of information are being sought: First, can we define cell surface molecules, physical changes or intracellular events that define different stages of differentiation in CD4+ T cells, allowing us to place a given cell in a given activation state, and also allowing the measurement of transitions from one stats to another? Second, what are the requirements, both in terms of ligand and in terms of accessory cells or molecules derived from accessory cells, needed to drive a resting CD4+ T cell to memory or effector cells? Third, how do requirements for priming of D4+ T cells to become helper or inflammatory T cells differ? Finally, how do the activation requirements of T cells in different states of differentiation differ from one another, and what is the mechanism of this change? To carry out these studies, we will use monoclonal antibodies to the T cell receptor bound to cells or to plastic, or in soluble form, to stimulate resting or activated CD4+ T cells or cloned T cell lines representing different states of activation and different functional phenotypes, and compare activation requirements. Such assays will be used to identify and purify accessory cell molecules that contribute to in vitro priming. Monoclonal antibodies will be raised against these accessory cell factors and against cell surface molecules on cells in different states of activation so that we can accurately define activation state.

最免疫响应的最关键事件 是通过抗原激活静止的CD4+ T细胞。 这个步骤 在免疫反应中似乎不仅需要表现 T细胞受体的足够配体，但附件信号 也是如此。 此步骤导致了内存的产生和 效应T细胞。 免疫反应的这一步骤非常困难 详细分析，因为它没有有效地模仿 体外，通常通过体内抗原启动进行研究。 本研究的目的是使用抗T细胞受体 抗体作为抗原的替代品，并表征启动 使用各种检测系统的T细胞的T细胞，其中一些可能 不需要T细胞增殖。 四种不同类型的 正在寻找信息：首先，我们可以定义细胞表面 分子，物理变化或定义的细胞内事件 CD4+ T细胞中分化的不同阶段，使我们 将给定的单元放在给定的激活状态下，也将 允许测量从一个统计数据到另一个统计数据的过渡？ 第二，无论是在配体还是在 辅助细胞或辅助细胞的分子的术语， 需要将静止的CD4+ T细胞驱动到内存或效应细胞吗？ 第三，如何启动D4+ T细胞的需求成为 助手或炎性T细胞不同？ 最后，如何 T细胞在不同状态的激活要求 分化彼此不同，机制是什么 这个变化？ 为了进行这些研究，我们将使用单克隆抗体 T细胞受体结合到细胞或塑料或可溶性 形成，刺激静息或激活的CD4+ T细胞或克隆T 表示不同激活状态的细胞系和 不同的功能表型并比较激活 要求。 此类测定将用于识别和净化 辅助细胞分子有助于体外启动。 单克隆抗体将针对这些辅助细胞提出 因素和针对不同细胞上细胞表面分子的因素 激活状态，以便我们可以准确定义激活 状态。