Full activation of the T cell receptor requires both clustering and conformational changes at CD3
Full activation of the T cell receptor requires both clustering and conformational changes at CD3
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DOI：
10.1016/j.immuni.2006.10.019
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发表时间：
2007-01-01
期刊：
影响因子：
32.4
通讯作者：
Schamel, Wolfgang W. A.
中科院分区：
文献类型：
--
作者：
Minguet, Susana;Swamy, Mahima;Schamel, Wolfgang W. A.
T细胞受体(TCR-CD3)的触发既涉及受体聚集，也涉及CD3亚单位胞浆尾部的构象变化。TCRα-β配体结合导致CD3构象改变的机制尚不清楚。通过使用定义明确的配体，我们证明了诱导构象变化既需要多价结合，也需要质膜对TCR-CD3的迁移率限制。这种构象变化是由两个TCR-CD3复合体的协同重排引起的，不需要伴随TCRα-β外区结构的变化。CD3的这种构象变化在配体解离后逆转，是T细胞激活所必需的。因此，我们的许可几何模型提供了一种分子机制，使与TCRαβ结合的配体信息如何传递到CD3亚基和细胞内信号机制。
T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits. The mechanism by which TCR alpha beta ligand binding confers conformational changes to CD3 is unknown. By using well-defined ligands, we showed that induction of the conformational change requires both multivalent engagement and the mobility restriction of the TCR-CD3 imposed by the plasma membrane. The conformational change is elicited by cooperative rearrangements of two TCR-CD3 complexes and does not require accompanying changes in the structure of the TCR alpha beta ectodomains. This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation. Thus, our permissive geometry model provides a molecular mechanism that rationalizes how the information of ligand binding to TCR alpha beta is transmitted to the CD3 subunits and to the intracellular signaling machinery.