Receptor proximity, not intermolecular orientation, is critical for triggering T-cell activation
Receptor proximity, not intermolecular orientation, is critical for triggering T-cell activation
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DOI：
10.1074/jbc.m103280200
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发表时间：
2001-07-27
影响因子：
4.8
通讯作者：
Stern, LJ
中科院分区：
文献类型：
--
作者：
Cochran, JR;Cameron, TO;Stern, LJ
T细胞表面上的抗原受体与结合至主要组织相容性复合体（MHC）蛋白的肽的接合以涉及受体寡聚化的机制触发T细胞活化。通过可溶性MHC寡聚体的受体二聚化足以诱导T细胞中的几种特征性活化过程，包括接合受体的内化和细胞表面蛋白的上调。在这项工作中，活化受体二聚体内的分子间取向的影响进行了研究。以各种方向和拓扑结构偶联的II类MHC蛋白的二聚体都能够激活CD 4（+）T细胞，表明触发不依赖于特定的受体方向。与受体取向的最小影响相反，T细胞触发受MHC分子之间的分子间距离的影响，并且通过shot-ter交联剂偶联的MHC二聚体始终比通过较长交联剂偶联的那些更有效。这些结果与分子间受体接近而非分子间取向是抗原诱导的CD 4（+）T细胞活化的关键决定因素的机制一致。
Engagement of antigen receptors on the surface of T-cells with peptides bound to major histocompatibility complex (MHC) proteins triggers T-cell activation in a mechanism involving receptor oligomerization. Receptor dimerization by soluble MHC oligomers is sufficient to induce several characteristic activation processes in T-cells including internalization of engaged receptors and up-regulation of cell surface proteins. In this work, the influence of intermolecular orientation within the activating receptor dimer was studied. Dimers of class II MHC proteins coupled in a variety of orientations and topologies each were able to activate CD4(+) T-cells, indicating that triggering was not dependent on a particular receptor orientation. In contrast to the minimal influence of receptor orientation, T-cell triggering was affected by the inter-molecular distance between MHC molecules, and MHC dimers coupled through shot-ter cross-linkers were consistently more potent than those coupled through longer cross-linkers. These results are consistent with a mechanism in which intermolecular receptor proximity, but not intermolecular orientation, is the key determinant for antigen-induced CD4(+) T-cell activation.