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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >T cell receptor-ligand interactions: A conformational preequilibrium or an induced fit
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T cell receptor-ligand interactions: A conformational preequilibrium or an induced fit

机译：T细胞受体-配体相互作用：构象平衡前或诱导的契合

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Kinetic parameters of T cell receptor (TCR) interactions with its ligand have been proposed to control T cell activation. Analysis of kinetic data obtained has so far produced conflicting insights; here, we offer a consideration of this problem. As a model system, association and dissociation of a soluble TCR (sT1) and its specific ligand, an azidobenzoic acid derivative of the peptide SYIPSAEK-(ABA)1 (residues 252-260 from Plasmodium berghei circumsporozoite protein), bound to class 1 MHC H-2K(d)-encoded molecule (MHCp) were studied by surface plasmon resonance. The association time courses exhibited biphasic patterns. The fast and dominant phase was assigned to ligand association with the major fraction of TCR molecules, whereas the slow component was attributed to the presence of traces of TCR dimers. The association rate constant derived for the fast phase, assuming a reversible, single-step reaction mechanism, was relatively slow and markedly temperature-dependent, decreasing from 7.0 x 10(3) at 25degreesC to 1.8 x 10(2) M(-1.)s(-1) at 4degreesC. Hence, it is suggested that these observed slow rate constants are the result of unresolved elementary steps of the process. indeed, our analysis of the kinetic data shows that the time courses of TCR-MHCp interaction fit well to two different, yet closely related mechanisms, where an induced fit or a preequilibrium of two unbound TCR conformers are operational. These mechanisms may provide a rationale for the reported conformational flexibility of the TCR and its unusual ligand recognition properties, which combine high specificity with considerable cross-reactivity.
机译：已经提出了T细胞受体（TCR）与其配体相互作用的动力学参数以控制T细胞活化。迄今为止，获得的动力学数据分析产生了相互矛盾的见解。在这里，我们考虑这个问题。作为模型系统，可溶的TCR（sT1）及其特异性配体，SYIPSAEK-（ABA）1肽（来自伯氏疟原虫环子孢子蛋白的残基252-260）的叠氮苯甲酸衍生物与1类MHC结合和解离通过表面等离振子共振研究了H-2K（d）编码的分子（MHCp）。关联时间课程显示出双相模式。快相和显性相被分配给与TCR分子主要部分的配体缔合，而慢相则归因于痕量TCR二聚体的存在。假设可逆的单步反应机理，快相的缔合速率常数相对较慢且明显依赖温度，在25℃时从7.0 x 10（3）降低至1.8 x 10（2）M（-1） 。）s（-1）在4摄氏度。因此，建议这些观察到的慢速常数是该方法未解决的基本步骤的结果。实际上，我们对动力学数据的分析表明，TCR-MHCp相互作用的时程非常适合两种不同但密切相关的机制，其中两个未结合的TCR构象异构体的诱导契合或预平衡是可行的。这些机制可能为TCR报道的构象灵活性及其不寻常的配体识别特性提供理论依据，这些特性将高特异性与可观的交叉反应性结合在一起。

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