The intersection of affinity and specificity in the development and optimization of T cell receptor based therapeutics.
The intersection of affinity and specificity in the development and optimization of T cell receptor based therapeutics.
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DOI：
10.1016/j.semcdb.2017.10.017
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发表时间：
2018-12
影响因子：
7.3
通讯作者：
Baker, Brian M.
中科院分区：
文献类型：
--
作者：
Riley, Timothy P.;Baker, Brian M.
关键词：
αβ T细胞受体（TCR）在识别免疫靶点和信号传导适当反应中的作用为令人兴奋的翻译提供了机会。然而，tcr介导了生物学中最复杂的蛋白质-蛋白质相互作用之一，复杂的信号传导和选择机制增加了额外的复杂性。在这篇综述中，我们讨论了这些复杂性如何影响基于tcr的治疗方法的开发和优化，重点是结构、亲和力和特异性之间的交叉。我们强调了TCRs和种系抗体在分子识别方面的相似性，但强调通过模拟抗体成熟来设计TCRs可能不会产生转化为改善的生物学结果。关键的一点是需要区分TCR生化识别和T细胞功能识别，以及这种区分对TCR工程努力的影响。我们建议从自然免疫中学习，利用结构特征和最先进的蛋白质设计原则作为优化tcr治疗用途的手段。
The role of the αβ T cell receptor (TCR) in identifying immunological targets and signaling appropriate responses provides for exciting translational opportunities. Yet TCRs mediate one of the most complex protein-protein interactions in biology, with intricate signaling and selection mechanisms adding additional layers of sophistication. In this review, we discuss how these complexities influence the development and optimization of TCR-based therapeutics, focusing on the intersection between structure, affinity, and specificity. We highlight similarities between TCRs and germline antibodies in molecular recognition, but emphasize that engineering TCRs by mimicking antibody maturation may not yield translate into improved biological outcomes. A key point is the need to distinguish TCR biochemical recognition from T cell functional recognition and the consequences this distinction has for efforts in TCR engineering. We suggest learning from natural immunity and taking advantage of structural features and state-of-the-art protein design principles as a means to optimize TCRs for therapeutic use.
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影响因子：
64.5
作者：
Birnbaum ME;Mendoza JL;Sethi DK;Dong S;Glanville J;Dobbins J;Ozkan E;Davis MM;Wucherpfennig KW;Garcia KC
通讯作者：
Garcia KC
影响因子：
7.3
作者：
Brazin KN;Mallis RJ;Das DK;Feng Y;Hwang W;Wang JH;Wagner G;Lang MJ;Reinherz EL
通讯作者：
Reinherz EL
DOI：
10.4049/jimmunol.1003150
发表时间：
2011-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Borbulevych OY;Piepenbrink KH;Baker BM
通讯作者：
Baker BM
影响因子：
56.9
作者：
Arstila, TP;Casrouge, A;Kourilsky, P
通讯作者：
Kourilsky, P
影响因子：
5.6
作者：
Chlewicki, LK;Holler, PD;Kranz, DM
通讯作者：
Kranz, DM