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

Le Nours, Jérôme, Gherardin, Nicholas A., Ramarathinam, Sri H., Awad, Wael, Wiede, Florian, Gully, Benjamin S., Khandokar, Yogesh, Praveena, T., Wubben, Jacinta M., Sandow, Jarrod J., Webb, Andrew I., von Borstel, Anouk, Rice, Michael T., Redmond, Samuel J., Seneviratna, Rebecca, Sandoval-Romero, Maria L., Li, Shihan, Souter, Michael N. T., Eckle, Sidonia B. G., Corbett, Alexandra J., Reid, Hugh H., Liu, Ligong, Fairlie, David P., Giles, Edward M., Westall, Glen P., Tothill, Richard W., Davey, Martin S., Berry, Richard, Tiganis, Tony, McCluskey, James, Pellicci, Daniel G., Purcell, Anthony W., Uldrich, Adam P., Godfrey, Dale I. and Rossjohn, Jamie 2019. A class of γδ T cell receptors recognize the underside of the antigen-presenting molecule MR1. Science 366 (6472) , pp. 1522-1527. 10.1126/science.aav3900

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Association for the Advancement of Science
ISSN: 0036-8075
Date of Acceptance: 21 November 2019
Last Modified: 17 Apr 2020 11:16

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