Disparate thermodynamics governing T cell receptor-MHC-I interactions implicate extrinsic factors in guiding MHC restriction
Disparate thermodynamics governing T cell receptor-MHC-I interactions implicate extrinsic factors in guiding MHC restriction
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DOI：
10.1073/pnas.0600743103
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发表时间：
2006-04-25
影响因子：
11.1
通讯作者：
Rossjohn, J
中科院分区：
文献类型：
--
作者：
Ely, LK;Beddoe, T;Rossjohn, J
主要组织相容性复合体（MHC）限制的基础尚不清楚。然而，目前的数据表明，一个共同的热力学签名决定α β T细胞受体（TcR）连接。为了评估这种热力学特征是否定义了MIHC限制，我们研究了高度表征的免疫显性TcR与其同源肽-MHC-I配体相互作用的热力学基础。令人惊讶的是，我们观察到这种相互作用由有利的熵力和熵力控制，这与普遍的普遍性相反，即，由熵力驱动的相互作用与明显不利的熵力相结合。我们的结论是外在的分子因素，如辅助受体连接，参与TcR信号传导的构象调整，或连接TcR的高阶排列所决定的约束，可能发挥更大的作用，在指导MHC限制比以前认识到。
The underlying basis of major histocompatibility complex (MHC) restriction is unclear. Nevertheless, current data suggest that a common thermodynamic signature dictates alpha beta T cell receptor (TcR) ligation. To evaluate whether this thermodynamic signature defines MIHC restriction, we have examined the thermodynamic basis of a highly characterized immunodominant TcR interacting with its cognate peptide-MHC-I ligand. Surprisingly, we observed this interaction to be governed by favorable enthalpic and entropic forces, which is in contrast to the prevailing generality, namely, enthalpically driven interactions combined with markedly unfavorable entropic forces. We conclude that extrinsic molecular factors, such as coreceptor ligation, conformational adjustments involved in TcR signaling, or constraints dictated by higher-order arrangement of ligated TcRs, might play a greater role in guiding MHC restriction than appreciated previously.