Journal
COMMUNICATIONS BIOLOGY
Volume 5, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-021-02995-1
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Funding
- Ministry of Science and Technology, Taipei, Taiwan [NSC99-2320-B-001-005-MY3]
- Kennedy Trust for Rheumatology Research
- UKRI-BBSRC grant [BB/M011224/1]
- Clarendon Fund (University of Oxford)
- Oxford Interdisciplinary Bioscience DTP
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This study proposes a TCR Bending Mechanosignal (TBM) model which suggests that local mechanical membrane bending of T cells on the nanometer scale may influence T cell receptor binding events and thus T-cell activation. The model highlights how the bending of the T cell membrane can enhance signaling and facilitate better recognition of antigens.
T cells are critically important for host defense against infections. T cell activation is specific because signal initiation requires T cell receptor (TCR) recognition of foreign antigen peptides presented by major histocompatibility complexes (pMHC) on antigen presenting cells (APCs). Recent advances reveal that the TCR acts as a mechanoreceptor, but it remains unclear how pMHC/TCR engagement generates mechanical forces that are converted to intracellular signals. Here we propose a TCR Bending Mechanosignal (TBM) model, in which local bending of the T cell membrane on the nanometer scale allows sustained contact of relatively small pMHC/TCR complexes interspersed among large surface receptors and adhesion molecules on the opposing surfaces of T cells and APCs. Localized T cell membrane bending is suggested to increase accessibility of TCR signaling domains to phosphorylation, facilitate selective recognition of agonists that form catch bonds, and reduce noise signals associated with slip bonds. Al-Aghbar et al propose a TCR bending mechanosignal model that demonstrates how local mechanical membrane bending may influence T cell receptor binding events and thus T-cell activation.
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