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CLASS II-IA EXPRESSION BY ACTIVATING T CELLS

通过激活 T 细胞表达 II-IA 类

基本信息

批准号：
3135737
负责人：
KAREN S ZIER
金额：
$ 15.69万
依托单位：
MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 1990-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3135737
关键词：
T lymphocyte antibody dependent killer cell gene expression genetic manipulation genetic transcription helper T lymphocyte histocompatibility antigens immunoregulation interleukin 2 leukocyte activation /transformation messenger RNA mutant tissue /cell culture

项目摘要

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.

在HLA复合体中编码的抗原在人类免疫系统中起重要作用。在控制免疫反应中的作用。目前，三大 HLA抗原的种类可以定义为：1）I类产品，由HLA-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，以及3）III类产品其编码参与补体级联的组分。 I类抗原由所有单核血细胞表达。然而，II类抗原具有有限的组织分布。它们由B细胞、单核细胞和活化的但而不是静止的T细胞。长期以来，人们已经认识到，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而言，它们在以下方面发挥着关键作用：抗原呈递，2）在T细胞之间的通信中， B细胞之间以及T细胞和巨噬细胞之间，以及3）影响对某些疾病的易感性。而II类表达由活化的T细胞还没有得到很好的研究，最近的证据表明，表明它们可能参与T细胞功能。为例如，据报道，增加抗II类单克隆抗体可抑制活化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。的该提案的主要目的是确定以下关系： II类基因表达和T细胞活化和功能。我们将通过研究《圣经》的转录来实现我们的目标1）三种类型的II类基因（DR，DQ，DP）与两种在T细胞活化过程中，IL-2分子及其受体（Tac），并与启动扩散，2）并通过检查是否有定性或II类mRNA积累的定量差异具有不同功能活性的T细胞克隆。阐明 II类基因表达的机制及意义活化的T细胞将对设计具有重要意义，基础研究中免疫调节的新方法，以及就像在临床环境中一样。