Journal article
Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers
TS Fulford, C Soliman, RG Castle, M Rigau, Z Ruan, O Dolezal, R Seneviratna, HG Brown, E Hanssen, A Hammet, S Li, SJ Redmond, A Chung, MA Gorman, MW Parker, O Patel, TS Peat, J Newman, A Behren, NA Gherardin Show all
Nature Immunology | Published : 2024
Abstract
Butyrophilin (BTN) molecules are emerging as key regulators of T cell immunity; however, how they trigger cell-mediated responses is poorly understood. Here, the crystal structure of a gamma-delta T cell antigen receptor (γδTCR) in complex with BTN2A1 revealed that BTN2A1 engages the side of the γδTCR, leaving the apical TCR surface bioavailable. We reveal that a second γδTCR ligand co-engages γδTCR via binding to this accessible apical surface in a BTN3A1-dependent manner. BTN2A1 and BTN3A1 also directly interact with each other in cis, and structural analysis revealed formation of W-shaped heteromeric multimers. This BTN2A1–BTN3A1 interaction involved the same epitopes that BTN2A1 and BTN3..
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Grants
Awarded by Victorian Cancer Agency
Funding Acknowledgements
We thank C. Panousis, G. Matthews and staff at CSL Limited for providing BTN2A1 monoclonal antibody, M. Hattarki from CSIRO for support with SPR, the C3 protein crystallization facility (CSIRO), the Ian Holmes Imaging Centre (Bio21 Institute, University of Melbourne), the MX beamlines at the Australian Synchrotron, the Melbourne Cytometry Platform (University of Melbourne) and AGRF. This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of ANSTO, and made use of the ACRF detector. Infrastructure support from the NHMRC Independent Research Institutes Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Support Program are gratefully acknowledged. Funding support was provided by the Miller Foundation Research Accelerator fund (to A.P.U.); the Cancer Council of Victoria 1126866 (to A.P.U.); the National Health and Medical Research Council of Australia 1184906 (to A.P.U.), 1165467 (to A.P.U.), 1194263 (to M.W.P.), 1117766 (to D.I.G.) and 2008913 (to D.I.G.); the Australian Research Council DP230102753 (A.P.U.), CE140100011 (to D.I.G.) and DE210100705 (to N.A.G.); a Cancer Council Victoria Postdoctoral Research Fellowship (to M.R.); and the Department of Health and Human Services acting through the Victorian Cancer Agency fellowship (to A.B.).