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.

抗原在HLA综合体内编码的抗原很重要在控制免疫反应中的作用。目前，三个主要可以定义HLA抗原的类：1）I类产品，由HLA-A，B和C位点编码，2）II（IA）产品，由HLA-DR，DQ和DP基因座以及3）III类产品编码涉及补充级联的组件的哪些代码。 I类抗原均由所有单核血细胞表达。但是，II类抗原的组织分布有限。它们由B细胞，单核细胞和激活表示，但不是通过静止的T细胞。长期以来一直认为，II类（IA）分子表达单核细胞和B细胞负责调节免疫系统。具体来说，他们扮演着关键角色1）抗原表现，2）在T细胞和T细胞之间的通信中 B细胞和T细胞和巨噬细胞之间，以及3）影响对某些疾病的敏感性。而II类表达活化的T细胞尚未得到很好的研究，最近的证据表明它们可能参与T细胞功能。为了例如，据报道添加了抗阶级II 单克隆抗体抑制了活化t的增殖细胞。这表明T细胞上的II类抗原可能影响触发电池的信号的传输增殖和功能能力的发展。这该提议的主要目的是定义 II类基因表达和T细胞激活和功能。我们将实现我们的目标1）研究三种类型的II类基因（DR，DQ，DP）相对于两个在T细胞激活期间，其他基因打开了IL-2分子及其受体（TAC），以及扩散，2），并检查是否存在定性或II类mRNA积累的定量差异由具有不同功能活性的T细胞克隆。阐明 II类基因表达在激活的T细胞将对设计具有重大影响基础研究中的免疫调节方法的新方法就像在临床环境中一样。