T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) interactions that result in T cell activation are complex and have been distinguished by their equilibrium affinity and kinetic profiles. While prior affinity-based models can successfully predict meaningful TCR-pMHC interactions in many cases, they occasionally fail at identifying TCR-pMHC interactions with low binding affinity. This study analyzes TCR-pMHC systems for which empirical kinetic and affinity data exist and prior affinity-based predictions have failed. We identify criteria for TCR-pMHC systems with available kinetic information where the introduction of a correction factor improves energy-based model predictions. This kinetic correction factor offers a means to refine existing models with additional data and offers molecular insights to help reconcile previously conflicting reports concerning the influence of TCR-pMHC binding kinetics and affinity on T cell activation.

中文翻译：

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将动力学数据整合到基于亲和力的模型中，以改进 T 细胞特异性预测


导致 T 细胞活化的 T 细胞受体 （TCR） 和肽主要组织相容性复合体 （pMHC） 相互作用很复杂，并且通过其平衡亲和力和动力学特征来区分。虽然先前基于亲和力的模型在许多情况下可以成功预测有意义的 TCR-pMHC 相互作用，但它们有时无法识别低结合亲和力的 TCR-pMHC 相互作用。本研究分析了存在经验动力学和亲和力数据且先前基于亲和力的预测失败的 TCR-pMHC 系统。我们确定了具有可用动力学信息的 TCR-pMHC 系统的标准，其中校正因子的引入改善了基于能量的模型预测。这种动力学校正因子提供了一种使用额外数据改进现有模型的方法，并提供了分子见解，以帮助协调以前关于 TCR-pMHC 结合动力学和亲和力对 T 细胞活化影响的相互矛盾的报告。