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T cell antigen receptor and chain genes and MHC restriction

T细胞抗原受体和链基因以及MHC限制

基本信息

批准号：
61570235
负责人：
YANAGI Yusuke
金额：
$ 1.41万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570235/
关键词：
T cell receptor Antigen recognition Suppressor T cell 自己免疫疾患

项目摘要

1. The T cell receptor (TcR) is composed of <alpha> and <beta> chains. By transferring cloned and <beta> chain genes, it was established that this <alpha><beta> heterodimer is responsible for the dual specificity of T cells. However, it is still not known which amino acid residues are important in determining T cell specificities.In order to define important amino acid residues, we derived mutant T cell clones with altered specificities from an I-A^K reactive T cell clone, MS202. One mutant clone, E-3, was shown to respond to I-A^D and I-A^d as well as I-A^K. It seemed that this specificity change was due to the structural change of TcR in E-o as molecular weight of TcR was smaller in E-3 than in MS202. However, nucleotide sequences of TcR <alpha> and <beta> chain genes were identical between MS202 and E-3. It was found that E-3 has a defect in glycosylation. In addition, these two clones might express two kinds of TcR molecules with different chains. We are in a process of determining the cause of specificity change in E-3.2. All murine suppressor T cell clones examined were shown to express TcR <alpha> and <beta> chain genes. We are now in a process of cloning genes specifically expressed in suppressor T cells using the subtraction hybridization.3. The amount of mRNA coding for TcR <alpha> and <beta> chains was found to be almost constant whether T cells are activated by antigens or not.4. The TcR <beta> chain gene of NZW mice seems to contribute to the autoimmunity in (NZB x NZW)F_1 mice.

1. T细胞受体（TcR）由<α>和<β>链组成。通过转移克隆基因和β链基因，确定了该<α>β异二聚体负责T细胞的双重特异性。然而，尚不清楚哪些氨基酸残基对于确定T细胞特异性很重要。为了定义重要的氨基酸残基，我们从I-A^K反应性T细胞克隆MS202中衍生出具有改变的特异性的突变T细胞克隆。一个突变克隆 E-3 显示对 I-A^D 和 I-A^d 以及 I-A^K 做出反应。这种特异性变化似乎是由于 E-o 中 TcR 的结构变化所致，因为 E-3 中的 TcR 分子量比 MS202 中的小。然而，MS202和E-3之间的TcR<α>和<β>链基因的核苷酸序列是相同的。发现E-3存在糖基化缺陷。此外，这两个克隆可能表达两种具有不同链的TcR分子。我们正在确定 E-3.2 中特异性变化的原因。所有检查的小鼠抑制性 T 细胞克隆均显示表达 TcR <α> 和 <β> 链基因。我们现在正处于使用消减杂交技术克隆抑制性T细胞特异表达基因的过程中。3．发现无论T细胞是否被抗原激活，编码TcR<α>和<β>链的mRNA量几乎恒定。4． NZW 小鼠的 TcR <β> 链基因似乎有助于 (NZB x NZW)F_1 小鼠的自身免疫。