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

T细胞在主要组织相容性复合体(MHC)I类或Calss II类抗原的背景下识别抗原。此外，已知抑制性T细胞(Ts)通过I-J抗原施加的基因限制来抑制其他T细胞的反应，其基因尚未确定。已知上述两种遗传限制都是在环境MHC的影响下，T细胞在胸腺早期个体发育过程中适应性获得的。为了阐明MHC限制的起源，我们从正常、F_1和辐射小鼠骨髓嵌合体中制备了大量的T细胞克隆。用不同MHC单倍型的抗原提呈细胞刺激进行细胞筛选。在分析TCR和基因以及I-J分子表达的同时，研究了这些克隆在抗原和靶细胞相互作用方面的MHC限制性特异性。已经证明，TCR和I-J对同一T细胞克隆的限制性内切酶不一定是相同的，表明它们是由不同的基因控制的。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。该克隆在限制特异性上有顺序变化，提示T细胞成熟后可能会改变限制特异性。最后，我们用生化方法鉴定了二维凝胶中的I-J分子是由两个43K糖肽亚基组成的相对分子质量为86K的二聚体。该分子在骨髓嵌合体中的表达被发现与胸腺MHC相适应。

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.