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

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.

• Authors: 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
• Journal: Science (New York, N.Y.) (Science) Vol. 367 Issue 6478 (02 07 2020) ISSN: 1095-9203 [Electronic] United States
• PMID: 31919129 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Antigens, CD
• Antigens, Neoplasm
• BTN2A1 protein, human
• BTN3A1 protein, human
• Butyrophilins
• Ligands
• Receptors, Antigen, T-Cell, gamma-delta
• T-cell receptor Vdelta2, human
• T-cell receptor Vgamma9, human

Topics

• Antigens, CD (chemistry, immunology)
• Antigens, Neoplasm (immunology)
• Butyrophilins (chemistry, genetics, immunology)
• Cell Line, Tumor
• Humans
• Ligands
• Lymphocyte Activation
• Phosphorylation
• Protein Domains
• Protein Multimerization
• Receptors, Antigen, T-Cell, gamma-delta (immunology)
• T-Lymphocytes (immunology)