A Photo-Crosslinkable Biotin Derivative of the Phosphoantigen (E)-4-Hydroxy-3-Methylbut-2-Enyl Diphosphate (HMBPP) Activates V gamma 9V delta 2 T Cells and Binds to the HMBPP Site of BTN3A1

Mattarei, Andrea and Enzinger, Monika and Gu, Siyi and Karunakaran, Mohindar Murugesh and Kimmel, Brigitte and Berner, Nicole and Adams, Erin J. and Herrmann, Thomas and Amslinger, Sabine (2017) A Photo-Crosslinkable Biotin Derivative of the Phosphoantigen (E)-4-Hydroxy-3-Methylbut-2-Enyl Diphosphate (HMBPP) Activates V gamma 9V delta 2 T Cells and Binds to the HMBPP Site of BTN3A1. CHEMISTRY-A EUROPEAN JOURNAL, 23 (49). pp. 11945-11954. ISSN 0947-6539, 1521-3765

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Abstract

V gamma 9V delta 2 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 V gamma 9V delta 2 T cell antigen receptors (V gamma 9V delta 2 TCRs) on V gamma 9V delta 2 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 of 2 at 308nm 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 ligand 1. Thus, BioBP-HMBPP (2) is a suitable tool to identify co-ligands or receptors involved in PAg-mediated T cell activation.

Item Type: Article
Uncontrolled Keywords: (E)-1-HYDROXY-2-METHYL-BUT-2-ENYL 4-DIPHOSPHATE; PHOSPHORYLATED ANTIGENS; TUMOR-CELLS; PYROPHOSPHATE; STIMULATION; RECOGNITION; PRENYLTRANSFERASES; BIOSYNTHESIS; SYNTHASE; RECEPTOR; B30.2 domain; BTN3A1; HMBPP; phosphoantigen; photoaffinity label
Subjects: 500 Science > 540 Chemistry & allied sciences
Divisions: Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Dr. Sabine Amslinger
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Dec 2018 13:15
Last Modified: 11 Feb 2019 14:25
URI: https://pred.uni-regensburg.de/id/eprint/1195

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