CLASS II (IA) EXPRESSION BY ACTIVATED T CELLS

在人类白细胞抗原复合体中编码的抗原起着重要的作用 在控制免疫反应中的作用。目前，有三大 可以定义人类白细胞抗原的类别：1)I类产品， 由人类白细胞抗原A、B和C基因座编码，2)II(Ia)类产物， 由HLA-DR、DQ和DP基因座编码和3)III类产物 该代码用于补充级联中涉及的组件。 所有的单核血细胞都表达I类抗原。 然而，II类抗原的组织分布有限。 它们由B细胞、单核细胞和活化的BUT表达 而不是通过静息T细胞。 长期以来，人们一直意识到II(Ia)类分子表达 在单核细胞和B细胞上负责调节 免疫系统。具体地说，它们在以下方面发挥了关键作用 抗原递呈，2)T细胞和T细胞之间的通讯 B细胞和T细胞与巨噬细胞之间，以及3)在影响 易患某些疾病。而第二类表达式由 最近的证据表明，激活的T细胞还没有得到很好的研究 提示它们可能参与T细胞功能。为 例如，据报道，添加抗II类药物 单抗可抑制活化T细胞的增殖 细胞。这表明T细胞上的II类抗原可能 影响触发细胞的信号的传输 增殖和功能能力的发展。这个 这项建议的主要目的是界定 II类基因表达与T细胞活化和功能的关系。 我们将通过研究单词的转录来实现我们的目标 三种类型的II类基因(DR、DQ、DP)与两个 在T细胞激活过程中启动的其他基因，IL-2分子 和它的受体(Tac)，以及与启动 扩散，2)并通过检查是否有定性的 或数量上的差异积累的第II类基因的mRNA 通过具有不同功能活性的T细胞克隆。澄清 类风湿因子II类基因表达的机制及意义 活化的T细胞将对人类免疫系统的设计产生重大影响 基础研究中免疫调节的新方法 就像在临床环境中一样。

Antigens coded for within the HLA complex play an important role in the control of immune responses. Presently, three major classes of HLA antigens can be defined: 1) Class I products, coded for by the HLA-A,B, and C loci, 2) Class II (Ia) products, coded for by the HLA-DR,DQ and DP loci and 3) Class III products which code for components involved in the complement cascade. Class I antigens are expressed by all mononuclear blood cells. Class II antigens, however, have a limited tissue distribution. They are expressed by B cells, monocytes, and by activated but not by resting T cells. It has long been appreciated that Class II (Ia) molecules expressed on monocytes and B cells are responsible for the regulation of the immune system. Specifically, they play a critical role 1) in antigen presentation, 2) in the communication between T cells and B cells and between T cells and macrophages, and 3) in influencing susceptibility to certain diseases. While Class II expression by activated T cells has not been well studied, recent evidence suggests that they may be involved in T cell function. For example, it was reported that the addition of anti-Class II monoclonal antibodies inhibited the proliferation of activated T cells. This suggested that Class II antigens on T cells might influence the transmission of signals which trigger cell proliferation and the development of functional ability. The principal aim of this proposal is to define the relationship between Class II gene expression and T cell activation and function. We will achieve our goal 1) by studying the transcription of the three types of Class II genes (DR, DQ, DP) in relation to two other genes turned on during T cell activation, the IL-2 molecule and its receptor (Tac), and in relation to the initiation of proliferation, 2) and by examining whether there are qualitative or quantitative differences in the accumulation of Class II mRNA by T cell clones with different functional activities. Elucidating the mechanism and significance of Class II gene expression in activated T cells will have major implications on the design of new approaches for immunomodulation in basic research, as well as in clinical settings.