近日，澳大利亚莫纳什大学Nicole L. La Gruta等研究人员合作发现，肽-MHC上的典型T细胞受体对接对于T细胞信号传导至关重要。2021年6月4日，国际知名学术期刊《科学》发表了这一成果。

据研究人员介绍，T细胞受体（TCR）识别肽-主要组织相容性复合物（pMHC）的特征在于高度保守的对接极性。这种极性是否由识别或信号限制驱动仍不清楚。

使用来自初始小鼠CD8⁺T 细胞库（这能够识别H-2Db–NP366表位）的“逆转对接”TCRβ可变（TRBV）17⁺ TCR，研究人员证明它们无法支持T细胞活化和体内招募，这是逆转对接极性的直接结果，而不是TCR-pMHCI结合或成簇的特征。

典型的TCR-pMHCI对接将CD8/Lck最佳地定位到CD3复合物，这被逆转的TCR-pMHCI极性所阻止。将Lck与CD8分离能够规避对经典对接的需求。因此，一致的TCR-pMHC对接拓扑结构受T细胞信号限制的约束。

附：英文原文

Title: Canonical T cell receptor docking on peptide–MHC is essential for T cell signaling

Author: Pirooz Zareie, Christopher Szeto, Carine Farenc, Sachith D. Gunasinghe, Elizabeth M. Kolawole, Angela Nguyen, Chantelle Blyth, Xavier Y. X. Sng, Jasmine Li, Claerwen M. Jones, Alex J. Fulcher, Jesica R. Jacobs, Qianru Wei, Lukasz Wojciech, Jan Petersen, Nicholas R.J. Gascoigne, Brian D. Evavold, Katharina Gaus, Stephanie Gras, Jamie Rossjohn, Nicole L. La Gruta

Issue&Volume: 2021/06/04

Abstract: T cell receptor (TCR) recognition of peptide–major histocompatibility complexes (pMHCs) is characterized by a highly conserved docking polarity. Whether this polarity is driven by recognition or signaling constraints remains unclear. Using “reversed-docking” TCRβ-variable (TRBV) 17+ TCRs from the nave mouse CD8+ T cell repertoire that recognizes the H-2Db–NP366 epitope, we demonstrate that their inability to support T cell activation and in vivo recruitment is a direct consequence of reversed docking polarity and not TCR–pMHCI binding or clustering characteristics. Canonical TCR–pMHCI docking optimally localizes CD8/Lck to the CD3 complex, which is prevented by reversed TCR–pMHCI polarity. The requirement for canonical docking was circumvented by dissociating Lck from CD8. Thus, the consensus TCR–pMHC docking topology is mandated by T cell signaling constraints.

DOI: 10.1126/science.abe9124

Source: https://science.sciencemag.org/content/372/6546/eabe9124