Journal article

Butyrophilin 2A1 is essential for phosphoantigen reactivity by gamma delta T cells

Marc Rigau, Simone Ostrouska, Thomas S Fulford, Darryl N Johnson, Katherine Woods, Zheng Ruan, Hamish EG McWilliam, Christopher Hudson, Candani Tutuka, Adam K Wheatley, Stephen J Kent, Jose A Villadangos, Bhupinder Pal, Christian Kurts, Jason Simmonds, Matthias Pelzing, Andrew D Nash, Andrew Hammet, Anne M Verhagen, Gino Vairo Show all

Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2020

Abstract

Gamma delta (γδ) T cells are essential to protective immunity. In humans, most γδ T cells express Vγ9Vδ2+ T cell receptors (TCRs) that respond to phosphoantigens (pAgs) produced by cellular pathogens and overexpressed by cancers. However, the molecular targets recognized by these γδTCRs are unknown. Here, we identify butyrophilin 2A1 (BTN2A1) as a key ligand that binds to the Vγ9+ TCR γ chain. BTN2A1 associates with another butyrophilin, BTN3A1, and these act together to initiate responses to pAg. Furthermore, binding of a second ligand, possibly BTN3A1, to a separate TCR domain incorporating Vδ2 is also required. This distinctive mode of Ag-dependent T cell activation advances our understan..

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Grants

Awarded by Cancer Council of Victoria


Awarded by Australian Research Council (ARC)


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by ARC Future Fellowship


Awarded by NHMRC Senior Principal Research Fellowship


Awarded by Deutsche Forschungsgemeinschaft


Awarded by NHMRC Principal Research Fellowship


Awarded by ARC Discovery Early Career Researcher Award


Funding Acknowledgements

This work was supported by the Cancer Council of Victoria (1126866), the Australian Research Council (ARC; CE140100011, DP170102471), the National Health and Medical Research Council of Australia (NHMRC; 1165467, 1113293), and the Operational Infrastructure Support Program provided by the Victorian Government, Australia. A.P.U. was supported by an ARC Future Fellowship (FT140100278); A.B. is supported by a fellowship from the Department of Health and Human Services acting through the Victorian Cancer Agency; D.I.G. is supported by an NHMRC Senior Principal Research Fellowship (1117766); M.R. is supported by the Deutsche Forschungsgemeinschaft (GRK2168) and the University of Melbourne through the International Research and Research Training Fund; J.A.V. is supported by an NHMRC Principal Research Fellowship (1154502); H.E.G.M. is supported by an ARC Discovery Early Career Researcher Award (DE170100575) and the AMP Tomorrow Fund.