Department of Molecular and Cellular Physiology, Program in Immunology, Stanford University School of Medicine, CA, USA.
Immunol Rev. 2012 Nov;250(1):82-101. doi: 10.1111/imr.12006.
Molecular diversity lies at the heart of adaptive immunity. T-cell receptors and peptide-major histocompatibility complex molecules utilize and rely upon an enormous degree of diversity at the levels of genetics, chemistry, and structure to engage one another and carry out their functions. This high level of diversity complicates the systematic study of important aspects of T-cell biology, but recent technical advances have allowed for the ability to study diversity in a comprehensive manner. In this review, we assess insights gained into T-cell receptor function and biology from our increasingly precise ability to assess the T-cell repertoire as a whole or to perturb individual receptors with engineered reagents. We conclude with a perspective on a new class of high-affinity, non-stimulatory peptide ligands we have recently discovered using diversity-oriented techniques that challenges notions for how we think about T-cell receptor signaling.
分子多样性是适应性免疫的核心。T 细胞受体和肽-主要组织相容性复合物分子在遗传、化学和结构水平上利用并依赖于极大程度的多样性来相互作用并发挥其功能。这种高度多样性使得对 T 细胞生物学重要方面的系统研究变得复杂，但最近的技术进步使我们能够全面地研究多样性。在这篇综述中，我们评估了从我们日益精确地评估整个 T 细胞库的能力或用工程试剂干扰单个受体中获得的关于 T 细胞受体功能和生物学的见解。最后，我们从一个新的角度来看待我们最近使用多样性导向技术发现的一类具有高亲和力的非刺激性肽配体，这些配体挑战了我们对 T 细胞受体信号转导的看法。
