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On the origin and adaptive changes of genetic restriction molecules on T cells

T细胞遗传限制分子的起源和适应性变化

基本信息

批准号：
60440037
负责人：
TADA Tomio
金额：
$ 18.56万
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 (A)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1988
项目状态：
已结题

项目摘要

T cells recognize antigen in context of major histocompatibility complex (MHC) class I or calss II antigens. In addition, it has been known that suppressor T cells (Ts) suppress the responses of other T cells with a genetic restriction imposed by the I-J antigen, whose genes have not been identified. Both above genetic restrictions are known to be adaptively acquired by T cells during their early ontogeny in the thymus under the influence of environmental MHC.In order to elucidate the origin of MHC restrictions, we produced a large number of T cell clones from normal, F_1 and mice of radiation bone marrow chimeras. The cells were selected by the stimulation with antigen-presenting cells of different MHC haplotypes. The MHC restriction specificities of these clones with respect to antigen- and target cell interactions have been studied in parallel with the analysis of TcR and genes, and of expression of I-J molecules. It has been demonstrated that restriction-specificities of TcR and I-J on the same T cell clone are not necessarily identical, indicating that they are controlled by different genes. One of the T cell clones showed one and two genes rearranged in-frame, while only one gene was expressed on the cell surface. This clone had sequential changes in the restriction specificity suggesting that T cells may change restriction specificity after maturation. Finally we identified biochemically the I-J molecule in two dimensional gel as a molecular weight 86K dimer composed of two 43K glycopeptide subunits. The expression of this molecule in bone marrow chimeras was found to be adaptive to the thymic MHC.

T细胞在主要组织相容性复合体（MHC）I类或II类抗原的背景下识别抗原。此外，已知抑制性T细胞（Ts）抑制具有由I-J抗原施加的遗传限制的其它T细胞的应答，所述I-J抗原的基因尚未鉴定。为了阐明T细胞在胸腺发育早期受环境MHC影响而适应性地获得上述两种遗传限制，我们从正常小鼠、F_1代小鼠和辐射骨髓嵌合体小鼠中制备了大量T细胞克隆。通过用不同MHC单倍型的抗原呈递细胞刺激来选择细胞。这些克隆相对于抗原和靶细胞相互作用的MHC限制性特异性已经与TcR和基因的分析以及I-J分子的表达的分析平行地进行了研究。已经证明，TcR和I-J在同一T细胞克隆上的限制特异性不一定相同，表明它们由不同的基因控制。其中一个T细胞克隆显示一个和两个基因在框内重排，而只有一个基因在细胞表面表达。该克隆在限制性酶切特异性上有连续的变化，表明T细胞在成熟后可能改变限制性酶切特异性。最后，我们在二维凝胶中生化鉴定了I-J分子是由两个43 K糖肽亚基组成的分子量为86 K的二聚体。该分子在骨髓嵌合体中的表达被认为是适应胸腺MHC的。