Singh Nishant K, Riley Timothy P, Baker Sarah Catherine B, Borrman Tyler, Weng Zhiping, Baker Brian M
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556.
Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556; and.
J Immunol. 2017 Oct 1;199(7):2203-2213. doi: 10.4049/jimmunol.1700744.
T cell specificity emerges from a myriad of processes, ranging from the biological pathways that control T cell signaling to the structural and physical mechanisms that influence how TCRs bind peptides and MHC proteins. Of these processes, the binding specificity of the TCR is a key component. However, TCR specificity is enigmatic: TCRs are at once specific but also cross-reactive. Although long appreciated, this duality continues to puzzle immunologists and has implications for the development of TCR-based therapeutics. In this review, we discuss TCR specificity, emphasizing results that have emerged from structural and physical studies of TCR binding. We show how the TCR specificity/cross-reactivity duality can be rationalized from structural and biophysical principles. There is excellent agreement between predictions from these principles and classic predictions about the scope of TCR cross-reactivity. We demonstrate how these same principles can also explain amino acid preferences in immunogenic epitopes and highlight opportunities for structural considerations in predictive immunology.
T细胞特异性源自众多过程，从控制T细胞信号传导的生物学途径到影响TCR如何结合肽和MHC蛋白的结构和物理机制。在这些过程中，TCR的结合特异性是关键组成部分。然而，TCR特异性却很神秘：TCR既具有特异性又具有交叉反应性。尽管这一点早已为人所知，但这种双重性仍然困扰着免疫学家，并对基于TCR的治疗方法的开发产生影响。在这篇综述中，我们讨论TCR特异性，重点介绍TCR结合的结构和物理研究中出现的结果。我们展示了如何从结构和生物物理原理来解释TCR特异性/交叉反应性的双重性。这些原理的预测与关于TCR交叉反应范围的经典预测之间存在极好的一致性。我们证明了这些相同的原理也可以解释免疫原性表位中的氨基酸偏好，并强调了预测性免疫学中结构考虑的机会。
