Projects per year
Abstract
Vγ9Vδ2 T cells play critical roles in microbial immunity by detecting target cells exposed to pathogen-derived phosphoantigens (P-Ags). Target cell expression of BTN3A1, the "P-Ag sensor," and BTN2A1, a direct ligand for T cell receptor (TCR) Vγ9, is essential for this process; however, the molecular mechanisms involved are unclear. Here, we characterize BTN2A1 interactions with Vγ9Vδ2 TCR and BTN3A1. Nuclear magnetic resonance (NMR), modeling, and mutagenesis establish a BTN2A1-immunoglobulin V (IgV)/BTN3A1-IgV structural model compatible with their cell-surface association in cis. However, TCR and BTN3A1-IgV binding to BTN2A1-IgV is mutually exclusive, owing to binding site proximity and overlap. Moreover, mutagenesis indicates that the BTN2A1-IgV/BTN3A1-IgV interaction is non-essential for recognition but instead identifies a molecular surface on BTN3A1-IgV essential to P-Ag sensing. These results establish a critical role for BTN3A-IgV in P-Ag sensing, in mediating direct or indirect interactions with the γδ-TCR. They support a composite-ligand model whereby intracellular P-Ag detection coordinates weak extracellular germline TCR/BTN2A1 and clonotypically influenced TCR/BTN3A-mediated interactions to initiate Vγ9Vδ2 TCR triggering.
Original language | English |
---|---|
Article number | 112321 |
Journal | Cell Reports |
Volume | 42 |
Issue number | 4 |
Early online date | 28 Mar 2023 |
DOIs | |
Publication status | Published - 25 Apr 2023 |
Bibliographical note
Copyright © 2023 The Authors. Published by Elsevier Inc.Keywords
- γδ
- T cell
- phosphoantigen
- butyrophilin
- nuclear magnetic resonance
Fingerprint
Dive into the research topics of 'Phosphoantigen sensing combines TCR-dependent recognition of the BTN3A IgV domain and germline interaction with BTN2A1'. Together they form a unique fingerprint.Projects
- 2 Active
-
Exploring innate-like and adaptive gamma delta T cell paradigms in health and disease
Owen, D., Dafforn, T., Mohammed, F. & Willcox, B.
1/03/21 → 28/02/26
Project: Research
-
HWB-NMR: a national resource for biomolecular research
Tennant, D., Young, S., Lavery, G., Peet, A., Ludwig, C., Futterer, K., Guenther, U., Henderson, I., Willcox, B., Adams, D. & Carlomagno, T.
25/09/17 → 25/09/24
Project: Research