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: 3140788
• 负责人: CHARLES A JANEWAY
• 金额: $ 17.09万
• 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/3140788
• 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.

诱导最强免疫反应的最关键事件 是抗原激活静息 CD4+ T 细胞。 这一步 在免疫反应中似乎不仅需要呈现 足够的 T 细胞受体配体，但有辅助信号 以及。 这一步导致了内存和 效应T细胞。 免疫反应的这一步非常困难 详细分析，因为它还没有被有效模仿 体外，通常通过用抗原进行体内引发来研究。 目前研究的目标是使用抗T细胞受体 抗体作为抗原的替代品，并表征引发 使用多种检测系统检测 T 细胞，其中一些可能 不需要T细胞增殖。 四种不同类型 正在寻求信息：首先，我们可以定义细胞表面吗 分子、物理变化或细胞内事件定义 CD4+ T 细胞的不同分化阶段，使我们能够 将给定单元置于给定激活状态，并且 允许测量从一种统计数据到另一种统计数据的转换？ 其次，在配体和在方面有什么要求？ 术语辅助细胞或源自辅助细胞的分子， 需要将静止的 CD4+ T 细胞驱动为记忆细胞或效应细胞吗？ 第三，D4+ T细胞的启动要求如何变得 辅助性T细胞或炎症性T细胞有何不同？ 最后，如何 不同状态下T细胞的激活要求 分化程度各不相同，其机制是什么 这个变化？ 为了进行这些研究，我们将使用单克隆抗体 T 细胞受体与细胞、塑料或可溶性物质结合 形式，刺激静息或激活的 CD4+ T 细胞或克隆 T 细胞 代表不同激活状态的细胞系 不同的功能表型，并比较激活 要求。 此类测定将用于识别和纯化 有助于体外启动的辅助细胞分子。 将针对这些辅助细胞产生单克隆抗体 不同细胞上的因子和针对细胞表面分子的作用 激活状态，以便我们可以准确定义激活 状态。