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ANTIGEN RECEPTOR GENES FROM TH AND TS CELLS

TH 和 TS 细胞的抗原受体基因

基本信息

批准号：
3132980
负责人：
ELLEN KRAIG
金额：
$ 14.96万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-04-01 至 1992-09-30
项目状态：
已结题

项目摘要

The long-term goal of this project is to understand how B cells and T cells interact in order to regulate an immune response. Using recombinant DNA techniques, we will isolate genes encoding antigen receptors from B cells and several subsets of T cells, all of which recognize the same antigen, the synthetic polypeptide, GAT. Several classes of GAT-specific lymphocytes have been cloned; they can be manipulated both in vivo and in vitro. These include: B cells, helper T (TH) cells and 3 subsets of suppressor T (Ts) cells. The B cell response to GAT is quite restricted in diversity. The receptor genes from GAT-TH cells are being characterized using T cell receptor (TcR) probes; we will determine whether there is a bias in the T cell repertoire for GAT, analogues to the B cell response to this antigen. Additionally, we have shown that some Ts cells transcribe TcR genes; we will characterize the organization, expression, and functional potential of TcR alpha, beta, and gamma genes in Ts cells. However, many Ts cells do not seem to use the beta chain of the TcR. We will clone the receptor genes from these cells by screening cDNA libraries with three different probes: 1) oligonucleotide probes predicted from protein sequences obtained for the antigen-binding factors secreted by Ts cells; 2) serological reagents directed against the I-J, Tsu/Tind, and idiotypic determinants on Ts cells and their factors; and 3) subtractive probes enriched for Ts transcripts. The receptor genes used by Ts cell have never been cloned; they will be mapped, characterized, and compared to the receptors used by TH and B cells specific for the same antigen. By comparing the genetic sequences used by the various lymphocyte classes to encode GAT-binding polypeptides, we will be in a unique position to study the molecular bases of antigen recognition and MHC restriction. Since the cells have been cloned, we will be able to determine the role of the receptors in immune cellular regulation and lymphocyte activation. A better understanding of the molecular controls operating in immune regulation is of primary importance in determining the basic mechanisms and defects in certain immune deficiency diseases and autoimmune disorders.

这个项目的长期目标是了解B细胞和T细胞相互作用以调节免疫反应。利用重组DNA技术，我们将分离出编码来自B细胞和T细胞的几个亚群的抗原受体细胞，所有这些都识别相同的抗原，合成的多肽，GAT。几类GAT特异性淋巴细胞已经被克隆;它们可以在体内和体内被操纵。体外这些细胞包括：B细胞、辅助性T（TH）细胞和3个亚群，抑制性T细胞。 B细胞对GAT的反应相当限制多样性。 GAT-TH细胞的受体基因正在使用T细胞受体（TcR）探针进行表征;我们将确定T细胞库中是否存在对 GAT，类似于B细胞对该抗原的反应。此外，我们已经表明，一些Ts细胞转录TcR，基因;我们将描述组织，表达， Ts中TcR α、β和γ基因的功能潜力细胞然而，许多Ts细胞似乎不使用β链的TcR。我们将从这些细胞中克隆受体基因，用三种不同的探针筛选cDNA文库：1）从获得的蛋白质序列预测的寡核苷酸探针 Ts细胞分泌的抗原结合因子; 2）血清学针对I-J、大津/Tind和独特型的试剂 Ts细胞及其因子上的决定子;和3）减法富集Ts转录物的探针。 Ts使用的受体基因细胞从来没有被克隆过;它们将被绘制，表征，并与TH和B细胞特异性使用的受体相比，相同的抗原。通过比较编码GAT结合的各种淋巴细胞类别多肽，我们将在一个独特的位置，研究抗原识别和MHC限制的分子基础。由于细胞已经克隆，我们将能够确定受体在免疫细胞调节中的作用，淋巴细胞活化更好地理解分子在免疫调节中起作用的控制是最重要的在确定的基本机制和缺陷，免疫缺陷疾病和自身免疫性疾病。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Suppressor cells and immunity.

抑制细胞和免疫。

DOI：
10.1159/000319224
发表时间：
1994
期刊：
Chemical immunology
影响因子：
0
作者：
Webb,DR;Kraig,E;Devens,BH
通讯作者：
Devens,BH

Binding of thymic factors to the conserved decanucleotide promoter element of the T-cell receptor V beta gene is developmentally regulated and is absent in SCID mice.

胸腺因子与 T 细胞受体 V beta 基因的保守十核苷酸启动子元件的结合受到发育调节，并且在 SCID 小鼠中不存在。

DOI：
10.1073/pnas.88.18.8131
发表时间：
1991
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Lanier,ER;Brown,RM;Kraig,E
通讯作者：
Kraig,E

Two ultraviolet tumor-specific suppressor cell clones. One expresses Ig RNA and the other expresses T cell receptor-alpha and -beta RNA.

两个紫外线肿瘤特异性抑制细胞克隆。