Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells.

Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells.

Science (New York, N.Y.) (2020-01-11)

Marc Rigau, Simone Ostrouska, Thomas S Fulford, Darryl N Johnson, Katherine Woods, Zheng Ruan, Hamish E G 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, Eugene Maraskovsky, Con Panousis, Nicholas A Gherardin, Jonathan Cebon, Dale I Godfrey, Andreas Behren, Adam P Uldrich

PMID31919129

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 understanding of diseases involving pAg recognition and creates opportunities for the development of γδ T cell-based immunotherapies.

MATERIALS

Product Number

Brand

Product Description

M6035

Sigma-Aldrich

4-(N-Maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt, powder