A seminal discovery of major histocompatibility complex (MHC) restriction in T cell recognition by Peter Doherty and Rolf Zinkernagel has led to 45 years of exciting research on the mechanisms governing peptide MHC (pMHC) recognition by T cell receptors (TCRs) and their importance in health and disease. T cells provide a significant level of protection against viral, bacterial, and parasitic infections, as well as tumors, hence, the generation of protective T cell responses is a primary goal for cell-mediated vaccines and immunotherapies. Understanding the mechanisms underlying generation of optimal high-avidity effector T cell responses, memory development, maintenance, and recall is of major importance for the rational design of preventative and therapeutic vaccines/immunotherapies. In this review, we summarize the lessons learned over the last four decades and outline our current understanding of the basis and consequences of pMHC/TCR interactions on T cell development and function, and TCR diversity and composition, driving better clinical outcomes and prevention of viral escape. We also discuss the current models of T cell memory formation and determinants of immunodominant T cell responses in animal models and humans. As TCR composition and diversity can affect both the protective capacity of T cells and protection against viral escape, defining the spectrum of TCR selection has implications for improving the functional efficacy of effector T cell responsiveness and memory formation.

中文翻译：

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健康和疾病中主要组织相容性复合体和T细胞受体的ABC。

Peter Doherty和Rolf Zinkernagel在T细胞识别中主要组织相容性复合物（MHC）限制的开创性发现已导致45年激动人心的研究，涉及控制T细胞受体（TCR）识别肽MHC（pMHC）的机制及其重要性。健康和疾病。T细胞为病毒，细菌和寄生虫感染以及肿瘤提供了显着水平的保护，因此，保护​​性T细胞反应的产生是细胞介导的疫苗和免疫疗法的主要目标。对于合理设计预防和治疗性疫苗/免疫疗法，了解最佳高亲和力效应T细胞应答，记忆发育，维持和记忆力的产生机制至关重要。在这篇评论中 我们总结了过去四十年的经验教训，并概述了我们目前对pMHC / TCR相互作用对T细胞发育和功能以及TCR多样性和组成的基础和后果的了解，从而推动了更好的临床结果和预防病毒逃逸。我们还讨论了动物模型和人类中T细胞记忆形成的当前模型以及免疫显性T细胞反应的决定因素。由于TCR的组成和多样性会影响T细胞的保护能力和对病毒逃逸的保护，因此定义TCR选择的范围对改善效应T细胞反应性和记忆形成的功能功效具有重要意义。以及TCR的多样性和组成，可推动更好的临床结果并预防病毒逃逸。我们还讨论了动物模型和人类中T细胞记忆形成的当前模型以及免疫显性T细胞反应的决定因素。由于TCR的组成和多样性会影响T细胞的保护能力和对病毒逃逸的保护，因此定义TCR选择的范围对改善效应T细胞反应性和记忆形成的功能功效具有重要意义。以及TCR的多样性和组成，可带来更好的临床效果并预防病毒逃逸。我们还讨论了动物模型和人类中T细胞记忆形成的当前模型以及免疫显性T细胞反应的决定因素。由于TCR的组成和多样性会影响T细胞的保护能力和对病毒逃逸的保护，因此定义TCR选择的范围对改善效应T细胞反应性和记忆形成的功能功效具有重要意义。