| Literature DB >> 31919129 |
Dale I Godfrey1,2, Andreas Behren3,4,5,6, Adam P Uldrich1,2, Marc Rigau7,8,2, Simone Ostrouska9,4, Thomas S Fulford7, Darryl N Johnson7,2, Katherine Woods9,4,5, Zheng Ruan7,2, Hamish E G McWilliam7,10, Christopher Hudson5, Candani Tutuka9,4, Adam K Wheatley7,11, Stephen J Kent7,11, Jose A Villadangos7,10, Bhupinder Pal9,4, Christian Kurts8, Jason Simmonds12, Matthias Pelzing12, Andrew D Nash12, Andrew Hammet12, Anne M Verhagen12, Gino Vairo12, Eugene Maraskovsky12, Con Panousis12, Nicholas A Gherardin7, Jonathan Cebon9,4,5,6,13.
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.Entities:
Year: 2020 PMID： 31919129 DOI： 10.1126/science.aay5516
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728