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. 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

doi:10.1126/science.aav3900

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 journal › Article › Research › peer-review

93 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 language	English
Pages (from-to)	1522-1527
Number of pages	6
Journal	Science
Volume	366
Issue number	6472
DOIs	https://doi.org/10.1126/science.aav3900
Publication status	Published - 20 Dec 2019

Access to Document

10.1126/science.aav3900

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

@article{ab40bcf11b7448c7aa1b6d6299230807,

title = "A class of γδ T cell receptors recognize the underside of the antigen-presenting molecule MR1",

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.",

author = "{Le Nours}, J{\'e}r{\^o}me and Gherardin, {Nicholas A.} and Ramarathinam, {Sri H.} and Wael Awad and Florian Wiede and Gully, {Benjamin S.} and Yogesh Khandokar and T. Praveena and Wubben, {Jacinta M.} and Sandow, {Jarrod J.} and Webb, {Andrew I.} and {von Borstel}, Anouk and Rice, {Michael T.} and Redmond, {Samuel J.} and Rebecca Seneviratna and Sandoval-Romero, {Maria L.} and Shihan Li and Souter, {Michael N.T.} and Eckle, {Sidonia B.G.} and Corbett, {Alexandra J.} and Reid, {Hugh H.} and Ligong Liu and Fairlie, {David P.} and Giles, {Edward M.} and Westall, {Glen P.} and Tothill, {Richard W.} and Davey, {Martin S.} and Richard Berry and Tony Tiganis and James McCluskey and Pellicci, {Daniel G.} and Purcell, {Anthony W.} and Uldrich, {Adam P.} and Godfrey, {Dale I.} and Jamie Rossjohn",

year = "2019",

month = dec,

day = "20",

doi = "10.1126/science.aav3900",

language = "English",

volume = "366",

pages = "1522--1527",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science (AAAS)",

number = "6472",

}

Le Nours, J, Gherardin, NA, Ramarathinam, SH, Awad, W, Wiede, F, Gully, BS, Khandokar, Y, Praveena, T, Wubben, JM, Sandow, JJ, Webb, AI, von Borstel, A, Rice, MT, Redmond, SJ, Seneviratna, R, Sandoval-Romero, ML, Li, S, Souter, MNT, Eckle, SBG, Corbett, AJ, Reid, HH, Liu, L, Fairlie, DP, Giles, EM , Westall, GP, Tothill, RW, Davey, MS, Berry, R, Tiganis, T, McCluskey, J, Pellicci, DG, Purcell, AW, Uldrich, AP, Godfrey, DI & Rossjohn, J 2019, 'A class of γδ T cell receptors recognize the underside of the antigen-presenting molecule MR1', Science, vol. 366, no. 6472, pp. 1522-1527. https://doi.org/10.1126/science.aav3900

TY - JOUR

T1 - A class of γδ T cell receptors recognize the underside of the antigen-presenting molecule MR1

AU - Le Nours, Jérôme

AU - Gherardin, Nicholas A.

AU - Ramarathinam, Sri H.

AU - Awad, Wael

AU - Wiede, Florian

AU - Gully, Benjamin S.

AU - Khandokar, Yogesh

AU - Praveena, T.

AU - Wubben, Jacinta M.

AU - Sandow, Jarrod J.

AU - Webb, Andrew I.

AU - von Borstel, Anouk

AU - Rice, Michael T.

AU - Redmond, Samuel J.

AU - Seneviratna, Rebecca

AU - Sandoval-Romero, Maria L.

AU - Li, Shihan

AU - Souter, Michael N.T.

AU - Eckle, Sidonia B.G.

AU - Corbett, Alexandra J.

AU - Reid, Hugh H.

AU - Liu, Ligong

AU - Fairlie, David P.

AU - Giles, Edward M.

AU - Westall, Glen P.

AU - Tothill, Richard W.

AU - Davey, Martin S.

AU - Berry, Richard

AU - Tiganis, Tony

AU - McCluskey, James

AU - Pellicci, Daniel G.

AU - Purcell, Anthony W.

AU - Uldrich, Adam P.

AU - Godfrey, Dale I.

AU - Rossjohn, Jamie

PY - 2019/12/20

Y1 - 2019/12/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85077124708&partnerID=8YFLogxK

U2 - 10.1126/science.aav3900

DO - 10.1126/science.aav3900

M3 - Article

C2 - 31857486

AN - SCOPUS:85077124708

SN - 0036-8075

VL - 366

SP - 1522

EP - 1527

JO - Science

JF - Science

IS - 6472

ER -

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

Abstract

Access to Document

Other files and links

PTPs in the CNS control of WAT browning

ARC Centre of Excellence in Advanced Molecular Imaging

Australian Synchrotron

Macromolecular Crystallisation Facility

Cite this

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

Abstract

Access to Document

Other files and links

Projects

PTPs in the CNS control of WAT browning

ARC Centre of Excellence in Advanced Molecular Imaging

Equipment

Australian Synchrotron

Macromolecular Crystallisation Facility

Cite this