澳大利亚莫纳什大学Jamie Rossjohn、墨尔本大学Dale I. Godfrey等研究人员合作解析了一类γδT细胞受体识别抗原呈递分子MR1的底面结构。这一研究成果于2019年12月20日发表在国际学术期刊《科学》上。

研究人员报道了从外周血和组织中表现出对单态性MHC相关蛋白1（MR1）自反应性的人类γδT细胞的多样化群体。γδTCR–MR1–抗原复合物的晶体结构与所有其他TCR–MHC和类似TCR–MHC-I的复合物形成鲜明对比， 即γδTCR在MR1抗原结合裂口下结合，其中接触以MR1α3结构域为主。对于来自多个个体的多种MR1限制性γδTCR，研究人员观察到相似的反应模式。

因此，研究人员同时将MR1报道为人类γδT细胞的配体，并重新定义了TCR的识别参数。

据悉，T细胞受体（TCR）识别主要组织相容性复合体（MHC）和MHC I类分子提供的抗原。

附：英文原文

Title: A class of γδ T cell receptors recognize the underside of the antigen-presenting molecule MR1

Author: Jérme Le Nours, Nicholas A. Gherardin, Sri H. Ramarathinam, Wael Awad, Florian Wiede, Benjamin S. Gully, Yogesh Khandokar, T. Praveena, Jacinta M. Wubben, Jarrod J. Sandow, Andrew I. Webb, Anouk von Borstel, Michael T. Rice, Samuel J. Redmond, Rebecca Seneviratna, Maria L. Sandoval-Romero, Shihan Li, Michael N. T. Souter, Sidonia B. G. Eckle, Alexandra J. Corbett, Hugh H. Reid, Ligong Liu, David P. Fairlie, Edward M. Giles, Glen P. Westall, Richard W. Tothill, Martin S. Davey, Richard Berry, Tony Tiganis, James McCluskey, Daniel G. Pellicci, Anthony W. Purcell, Adam P. Uldrich, Dale I. Godfrey, Jamie Rossjohn

Issue&Volume: 2019/12/20

Abstract: T cell receptors (TCRs) recognize antigens presented by major histocompatibility complex (MHC) and MHC class I–like molecules. We describe a diverse population of human γδ T cells isolated from peripheral blood and tissues that exhibit autoreactivity to the monomorphic MHC-related protein 1 (MR1). The crystal structure of a γδTCR–MR1–antigen complex starkly contrasts with all other TCR–MHC and TCR–MHC-I-like complex structures. Namely, the γδTCR binds underneath the MR1 antigen-binding cleft, where contacts are dominated by the MR1 α3 domain. A similar pattern of reactivity was observed for diverse MR1-restricted γδTCRs from multiple individuals. Accordingly, we simultaneously report MR1 as a ligand for human γδ T cells and redefine the parameters for TCR recognition.

DOI: 10.1126/science.aav3900

Source:

https://science.sciencemag.org/content/366/6472/1522