COORDINATE CONTROL OF HUMAN IA ANTIGENS AND II CHAIN

作为T细胞受体的主要配体之一，II类主要 组织相容性抗原是唯一适合于控制两种 T细胞的分化和活化。Ia表达的差异 可以赋予独特的能力来删除体内的自我反应性T细胞 胸腺，或启动外周淋巴因子的级联反应。这两个都是 对肿瘤、感染性病原体和可溶性的免疫监测很重要 抗原。因此，我们调节免疫反应的能力 抗原的多样性最终取决于我们对第II类基因的理解 监管。这项建议的目的是研究协调监管 多个II类基因之间以及具有不变链的 吉恩。越来越多的证据表明，II类基因和不变量 基因有一些同源元件。相反，一些第二类基因也 有独特的监管要素。所有监管要素都可以 与核蛋白相互作用，核蛋白被认为是转录因子。 这项提议的目标是确定DNA结合蛋白 调节一种II类基因(DRAlpha)的基因也调节其他各种基因 第二类基因，以及不变链基因。为了实现这一目标， 相关的DNA结合蛋白也将被使用。每个DNA的能力 具有DRAlpha基因特异性的结合蛋白控制多发性 II类基因以及不变链基因的协同方式 将会被评估。这种类型的功能分析肯定会 确定II类基因是否由于共享而受到协调调控 DNA结合蛋白的特异性。

As one of the primary ligands for the T cell receptor, the Class II major histocompatibility antigens are uniquely suited to control both the differentiation and activation of T cells. Differences in Ia expression can confer unique capabilities to delete self-reactive T cells in the thymus, or to initiate lymphokine cascades in the periphery. Both of these important for immune surveillance of tumors, infectious agents and soluble antigens. Therefore our ability to modulate the immune response to a variety of antigens ultimately relies on our understanding of class II gene regulation. The goal of this proposal is study the coordinate regulation of multiple class II genes among themselves and with the invariant chain gene. Accumulative evidence suggests that class II genes and invariant gene share some homologous elements. Conversely, some class II genes also have unique regulatory elements. All of the regulatory elements can interact with nuclear proteins which are presume transcription factors. The objectives of this proposal are to determine if DNA-binding proteins that regulate one class II gene (DRalpha) also regulates various other class II genes, as well as the invariant chain gene. To achieve this, relevant DNA binding proteins will also be used. The ability of each DNA binding protein with specificity for the DRalpha gene to control multiple class II genes as well as the invariant chain gene in a coordinate fashion will be assessed. This type of functional analysis will definitely determine if class II genes are coordinately regulated due to shared specificity for DNA-binding proteins.