Thermodynamics of T-cell receptor-peptide/MHC interactions: progress and opportunities.
Thermodynamics of T-cell receptor-peptide/MHC interactions: progress and opportunities.
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DOI：
10.1002/jmr.896
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发表时间：
2008-07
影响因子：
2.7
通讯作者：
Baker, Brian M.
中科院分区：
文献类型：
--
作者：
Armstrong, Kathryn M.;Insaidoo, Francis K.;Baker, Brian M.
关键词：
αβ T细胞受体（TCR）识别由I类或II类主要组织相容性复合物分子（pMHC）呈递的肽抗原。在这里，我们回顾了使用热力学测量在研究TCR-pMHC相互作用，注意结合热力学的多样性，这是如何与TCR-pMHC接口的变化。我们发现，有TCR结合没有焓或熵签名，相反，焓和熵的变化以补偿的方式，反映了一个狭窄的自由能窗口的相互作用，其特征在于。结合焓变和熵变与TCR-pMHC界面内的埋表面积或氢键数等结构特征不相关，可能反映了结合热力学的无数贡献者，但也可能反映了对范特霍夫量热测量的依赖以及与结合相关的平衡的未考虑的影响。TCR-pMHC结合热容量的变化同样变化很大。在某些情况下，热容量变化与结合和游离受体之间的构象差异一致，但几乎没有数据表明这些构象差异代表需要组织通常无序的CDR环。在这方面，我们讨论了热力学如何可能提供额外的洞察构象变化时发生TCR结合。最后，我们强调的机会，进一步使用热力学测量的研究TCR-pMHC的相互作用，不仅为了解TCR结合一般，但了解具体的个人相互作用和工程的T细胞受体所需的分子识别特性。
αβ T cell receptors (TCR) recognize peptide antigens presented by class I or class II major histocompatibility complex molecules (pMHC). Here we review the use of thermodynamic measurements in the study of TCR-pMHC interactions, with attention to the diversity in binding thermodynamics and how this is related to the variation in TCR-pMHC interfaces. We show that there is no enthalpic or entropic signature for TCR binding; rather, enthalpy and entropy changes vary in a compensatory manner that reflects a narrow free energy window for the interactions that have been characterized. Binding enthalpy and entropy changes do not correlate with structural features such as buried surface area or the number of hydrogen bonds within TCR-pMHC interfaces, possibly reflecting the myriad of contributors to binding thermodynamics, but likely also reflecting a reliance on van’t Hoff over calorimetric measurements and the unaccounted influence of equilibria linked to binding. TCR-pMHC binding heat capacity changes likewise vary considerably. In some cases the heat capacity changes are consistent with conformational differences between bound and free receptors, but there is little data indicating these conformational differences represent the need to organize commonly disordered CDR loops. In this regard, we discuss how thermodynamics may provide additional insight into conformational changes occurring upon TCR binding. Finally, we highlight opportunities for the further use of thermodynamic measurements in the study of TCR-pMHC interactions, not only for understanding TCR binding in general, but for understanding specifics of individual interactions and the engineering of T cell receptors with desired molecular recognition properties.
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影响因子：
6.8
作者：
Brady, GP;Sharp, KA
通讯作者：
Sharp, KA
影响因子：
2.9
作者：
Anikeeva, N;Lebedeva, T;Sykulev, Y
通讯作者：
Sykulev, Y
影响因子：
64.5
作者：
Colf, Leremy A.;Bankovich, Alexander J.;Garcia, K. Christopher
通讯作者：
Garcia, K. Christopher
DOI：
10.1073/pnas.0600743103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Ely, LK;Beddoe, T;Rossjohn, J
通讯作者：
Rossjohn, J
影响因子：
5.6
作者：
Gagnon, Susan J.;Borbulevych, Oleg Y.;Baker, Brian M.
通讯作者：
Baker, Brian M.