A Photo‐Crosslinkable Biotin Derivative of the Phosphoantigen (E)‐4‐Hydroxy‐3‐Methylbut‐2‐Enyl Diphosphate (HMBPP) Activates Vγ9Vδ2 T Cells and Binds to the HMBPP Site of BTN3A1. Issue 49 (10th August 2017)

• Record Type: Journal Article
• Authors: Mattarei, Andrea; Enzinger, Monika; Gu, Siyi; Karunakaran, Mohindar Murugesh; Kimmel, Brigitte; Berner, Nicole; Adams, Erin J.; Herrmann, Thomas; Amslinger, Sabine
• Is Part Of: Chemistry. Volume 23:Issue 49(2017)
• Page Start: 11945
• Page End: 11954
• Publication Date: 2017-08-10
• Subjects: B30.2 domain -- BTN3A1 -- HMBPP -- phosphoantigen -- photoaffinity label; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201702650
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Vγ9Vδ2 T cells play an important role in the cross talk of the innate and adaptive immune system. For their activation by phosphoantigens (PAgs), both cell surface receptors, the eponymous Vγ9Vδ2 T cell antigen receptors (Vγ9Vδ2 TCRs) on Vγ9Vδ2 T cells and butyrophilin 3A1 (BTN3A1) on the phosphoantigen‐"presenting" cell, are mandatory. To find yet undetected but further contributing proteins, a biotinylated, photo‐crosslinkable benzophenone probe BioBP‐HMBPP (2 ) was synthesized from a known allyl alcohol in nine steps and overall 16 % yield.2 is based on the picomolar PAg ( E )‐4‐hydroxy‐3‐methylbut‐2‐enyl diphosphate (HMBPP, 1 ). Laser irradiation of2 at 308 nm initiated the photo‐crosslinking reaction with proteins. When the B30.2 domain of BTN3A1, which contains a positively charged PAg‐binding pocket, was exposed to increasing amounts of HMBPP (1 ), labeling by BioBP‐HMBPP (2 ) was reduced significantly. Because BSA labeling was not impaired, 2 clearly binds to the same site as natural ligand1 . Thus, BioBP‐HMBPP (2 ) is a suitable tool to identify co‐ligands or receptors involved in PAg‐mediated T cell activation. Abstract : Catching phosphoantigen‐binding proteins : A hydrolytically stable photo‐crosslinkable probe "BioBP‐HMBPP" containing the phosphoantigen ( E )‐4‐hydroxy‐3‐methylbut‐2‐enyl diphosphate (HMBPP) was synthesized. By laser irradiation at 308 nm, the probe was crosslinked with the cell surface phosphoantigen receptor BTN3A1. This receptor is, amongst others, a crucial protein in the cross‐talk of the innate and adaptive immune system.