High-affinity T cell receptor differentiates cognate peptide-MHC and altered peptide ligands with distinct kinetics and thermodynamics.
High-affinity T cell receptor differentiates cognate peptide-MHC and altered peptide ligands with distinct kinetics and thermodynamics.
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DOI：
10.1016/j.molimm.2010.02.013
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发表时间：
2010-05
影响因子：
3.6
通讯作者：
Allen PM
中科院分区：
文献类型：
--
作者：
Persaud SP;Donermeyer DL;Weber KS;Kranz DM;Allen PM
T细胞受体和同源肽-MHC之间的相互作用是获得性免疫反应中至关重要的启动事件。这些结合事件是高度特异的，但以微摩尔亲和力发生。TCR和自身pMHC复合体之间更弱的相互作用在T细胞的发育、维持和共生活性中起着关键的调节作用。由于它们的低亲和力，这种弱相互作用的动力学和热力学很难研究。在这项工作中，我们使用了从3.L2 TCR系统中获得的高亲和力TCR M15，来研究两个改变的多肽配体(APL)的结合性质、热力学和特异性。我们对高亲和力TCR的亲和力测量支持这样的观点，即野生型TCR在毫米级亲和力范围内与这些APL结合，因此非常低的亲和力仍然可以引发生物学功能。最后，不同APL之间的单亚甲基差异导致了显著不同的结合热力学。PMHC抗原的这些微小变化与反应的熵和热焓的显著和不可预测的变化有关。由于相同的TCR是用几个结构相似的配体分析的，不同的热力学结合谱为T细胞受体如何实现精致的抗原特异性提供了一个机制视角。
Interactions between the T cell receptor and cognate peptide-MHC are crucial initiating events in the adaptive immune response. These binding events are highly specific yet occur with micromolar affinity. Even weaker interactions between TCR and self-pMHC complexes play critical regulatory roles in T cell development, maintenance and coagonist activity. Due to their low affinity, the kinetics and thermodynamics of such weak interactions are difficult to study. In this work, we used M15, a high-affinity TCR engineered from the 3.L2 TCR system, to study the binding properties, thermodynamics, and specificity of two altered peptide ligands (APLs). Our affinity measurements of the high-affinity TCR support the view that the wild type TCR binds these APLs in the millimolar affinity range, and hence very low affinities can still elicit biological functions. Finally, single methylene differences among the APLs gave rise to strikingly different binding thermodynamics. These minor changes in the pMHC antigen were associated with significant and unpredictable changes in both the entropy and enthalpy of the reaction. As the identical TCR was analyzed with several structurally similar ligands, the distinct thermodynamic binding profiles provide a mechanistic perspective on how exquisite antigen specificity is achieved by the T cell receptor.
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影响因子：
32.4
作者：
Ernst, B;Lee, DS;Surh, CD
通讯作者：
Surh, CD
DOI：
10.1084/jem.186.8.1223
发表时间：
1997-10-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brocker T
通讯作者：
Brocker T
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