Cutting Edge: Evidence for a Dynamically Driven T Cell Signaling Mechanism
Cutting Edge: Evidence for a Dynamically Driven T Cell Signaling Mechanism
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DOI：
10.4049/jimmunol.1200952
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发表时间：
2012-06-15
影响因子：
4.4
通讯作者：
Baker, Brian M.
中科院分区：
文献类型：
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作者：
Hawse, William F.;Champion, Matthew M.;Baker, Brian M.
T细胞利用ab TCR结合由MHC蛋白呈递的肽（pMHC）在apc上。TCR-pMHC复合物的形成通过一个鲜为人知的过程启动T细胞信号传导，可能涉及低聚物状态的改变、与CD3亚基相互作用的改变以及机械应力。这些机制可以通过结合诱导的TCR改变来促进，但任何这种改变的性质和程度尚不清楚。利用氢/氘交换，我们证明了连接整体刚性TCR，这将通过熵和包装效应促进与邻近蛋白质的结合，并增强现有配合物的稳定性。TCR区域涉及横向关联和信号特别受影响。计算模型表明，TCR常数和可变域之间的高度动态耦合在连接时受到抑制。这些结果提高了TCR触发可能涉及动态驱动的变构机制的可能性。中华免疫学杂志，2012,18(8):519 - 523。
T cells use the ab TCR to bind peptides presented by MHC proteins (pMHC) on APCs. Formation of a TCR-pMHC complex initiates T cell signaling via a poorly understood process, potentially involving changes in oligomeric state, altered interactions with CD3 subunits, and mechanical stress. These mechanisms could be facilitated by binding-induced changes in the TCR, but the nature and extent of any such alterations are unclear. Using hydrogen/deuterium exchange, we demonstrate that ligation globally rigidifies the TCR, which via entropic and packing effects will promote associations with neighboring proteins and enhance the stability of existing complexes. TCR regions implicated in lateral associations and signaling are particularly affected. Computational modeling demonstrated a high degree of dynamic coupling between the TCR constant and variable domains that is dampened upon ligation. These results raise the possibility that TCR triggering could involve a dynamically driven, allosteric mechanism. The Journal of Immunology, 2012, 188: 5819-5823.