Atypical T cell receptor signalling permits distinct gut gd T cell responses to healthy versus dysregulated tissues
- 1The Francis Crick Institute, Imperial College London
Abstract
Intraepithelial lymphocytes (IEL) are conserved across vertebrates and commonly enriched in {gamma}{delta} T cells. Several such {gamma}{delta} IELs depend upon homeostatic interactions of their T cell receptors (TCRs) with butyrophilin-like (BTNL) proteins expressed by healthy enterocytes and colonocytes. What limits such interactions from inducing full-blown T cell activation which would disrupt barrier integrity is unknown. Here, using primary IEL, we describe an atypical TCR signalling pathway (Signal 1) downstream of BTNL engagement, that fails to activate either global protein synthesis or cell proliferation. This attenuation could be overcome by provision of a co-stimulator (Signal 2) or inflammatory cytokines (Signal 3). It could also be relieved cell-intrinsically by blocking a lipid phosphatase. These findings can, at least in part, explain how extrinsic and intrinsic regulators permit IEL to be constitutively active in healthy tissues and additionally make full-blown responses to adaptive TCR ligands during tissue perturbation.
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BibTeX
@misc{monin2026atypical,
title = {{Atypical T cell receptor signalling permits distinct gut gd T cell responses to healthy versus dysregulated tissues}},
author = {L. Monin and F. Cano and J. Axford and G. Cooper and G. Hernandez-Mir and K. Okkenhaug and A. C. Hayday},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.757810},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757810v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Atypical T cell receptor signalling permits distinct gut gd T cell responses to healthy versus dysregulated tissues
AU - L. Monin
AU - F. Cano
AU - J. Axford
AU - G. Cooper
AU - G. Hernandez-Mir
AU - K. Okkenhaug
AU - A. C. Hayday
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.757810
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.757810v1
AB - Intraepithelial lymphocytes (IEL) are conserved across vertebrates and commonly enriched in {gamma}{delta} T cells. Several such {gamma}{delta} IELs depend upon homeostatic interactions of their T cell receptors (TCRs) with butyrophilin-like (BTNL) proteins expressed by healthy enterocytes and colonocytes. What limits such interactions from inducing full-blown T cell activation which would disrupt barrier integrity is unknown. Here, using primary IEL, we describe an atypical TCR signalling pathway (Signal 1) downstream of BTNL engagement, that fails to activate either global protein synthesis or cell proliferation. This attenuation could be overcome by provision of a co-stimulator (Signal 2) or inflammatory cytokines (Signal 3). It could also be relieved cell-intrinsically by blocking a lipid phosphatase. These findings can, at least in part, explain how extrinsic and intrinsic regulators permit IEL to be constitutively active in healthy tissues and additionally make full-blown responses to adaptive TCR ligands during tissue perturbation.
ER -