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

Jérôme 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. CorbettHugh 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

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1522-1527
Number of pages6
JournalScience
Volume366
Issue number6472
DOIs
Publication statusPublished - 20 Dec 2019

Cite this

Le Nours, J., Gherardin, N. A., Ramarathinam, S. H., Awad, W., Wiede, F., Gully, B. S., Khandokar, Y., Praveena, T., Wubben, J. M., Sandow, J. J., Webb, A. I., von Borstel, A., Rice, M. T., Redmond, S. J., Seneviratna, R., Sandoval-Romero, M. L., Li, S., Souter, M. N. T., Eckle, S. B. G., ... Rossjohn, J. (2019). A class of γδ T cell receptors recognize the underside of the antigen-presenting molecule MR1. Science, 366(6472), 1522-1527. https://doi.org/10.1126/science.aav3900