Affordable Access

deepdyve-link
Publisher Website

Butyrophilin-like 3 Directly Binds a Human Vγ4+ T Cell Receptor Using a Modality Distinct from Clonally-Restricted Antigen.

Authors
  • Willcox, Carrie R1
  • Vantourout, Pierre2
  • Salim, Mahboob1
  • Zlatareva, Iva2
  • Melandri, Daisy2
  • Zanardo, Leonor3
  • George, Roger4
  • Kjaer, Svend4
  • Jeeves, Mark5
  • Mohammed, Fiyaz1
  • Hayday, Adrian C6
  • Willcox, Benjamin E7
  • 1 Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Cancer Immunology and Immunotherapy Centre, University of Birmingham, Birmingham, UK.
  • 2 Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK; Immunosurveillance Laboratory, The Francis Crick Institute, London, UK.
  • 3 Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Cancer Immunology and Immunotherapy Centre, University of Birmingham, Birmingham, UK; Faculty of Medicine, University of Tours, Tours, France. , (France)
  • 4 Structural Biology Team, The Francis Crick Institute, London, UK.
  • 5 Henry Wellcome Building for NMR, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
  • 6 Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK; Immunosurveillance Laboratory, The Francis Crick Institute, London, UK. Electronic address: [email protected]
  • 7 Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Cancer Immunology and Immunotherapy Centre, University of Birmingham, Birmingham, UK. Electronic address: [email protected]
Type
Published Article
Journal
Immunity
Publication Date
Nov 19, 2019
Volume
51
Issue
5
Identifiers
DOI: 10.1016/j.immuni.2019.09.006
PMID: 31628053
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Butyrophilin (BTN) and butyrophilin-like (BTNL/Btnl) heteromers are major regulators of human and mouse γδ T cell subsets, but considerable contention surrounds whether they represent direct γδ T cell receptor (TCR) ligands. We demonstrate that the BTNL3 IgV domain binds directly and specifically to a human Vγ4+ TCR, "LES" with an affinity (∼15-25 μM) comparable to many αβ TCR-peptide major histocompatibility complex interactions. Mutations in germline-encoded Vγ4 CDR2 and HV4 loops, but not in somatically recombined CDR3 loops, drastically diminished binding and T cell responsiveness to BTNL3-BTNL8-expressing cells. Conversely, CDR3γ and CDR3δ loops mediated LES TCR binding to endothelial protein C receptor, a clonally restricted autoantigen, with minimal CDR1, CDR2, or HV4 contributions. Thus, the γδ TCR can employ two discrete binding modalities: a non-clonotypic, superantigen-like interaction mediating subset-specific regulation by BTNL/BTN molecules and CDR3-dependent, antibody-like interactions mediating adaptive γδ T cell biology. How these findings might broadly apply to γδ T cell regulation is also examined. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Report this publication

Statistics

Seen <100 times