<div class="csl-bib-body">
<div class="csl-entry">Schrangl, L., Kellner, F., Platzer, R., Mühlgrabner, V., Hubinger, P., Wieland, J., Obst, R., Toca-Herrera, J. L., Huppa, J. B., Schütz, G. J., & Göhring, J. (2025). CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions. <i>Nature Communications</i>, <i>16</i>(1), 757701–757714. https://doi.org/10.1038/s41467-025-62104-2</div>
</div>
-
dc.identifier.issn
2041-1723
-
dc.identifier.uri
http://hdl.handle.net/20.500.12708/225155
-
dc.description.abstract
Mechanical forces acting on ligand-engaged T-cell receptors (TCR) have previously been implicated in T-cell antigen recognition and ligand discrimination, yet their magnitude, frequency, and impact remain unclear. Here, we quantitatively assess forces across various TCR:pMHC pairs with different bond lifetimes at single-molecule resolution, both before and during T-cell activation, on platforms that either include or exclude tangential force registration. For this purpose, we use glass-supported lipid bilayers presenting pMHC conjugated to a molecular force sensor unit at its base, adhesion factors and costimulatory molecules to the approaching T-cells. Our results imply that CD4 + T-cell TCRs experience significantly lower forces than previously estimated, with only a small fraction of ligand-engaged TCRs being subjected to these forces during antigen scanning. These rare and minute mechanical forces do not impact the global lifetime distribution of the TCR:ligand bond. We propose that the immunological synapse is created as biophysically stable environment to prevent pulling forces from disturbing antigen recognition.
en
dc.language.iso
en
-
dc.publisher
NATURE PORTFOLIO
-
dc.relation.ispartof
Nature Communications
-
dc.subject
Lipid Bilayers
en
dc.subject
Humans
en
dc.subject
Lymphocyte Activation
en
dc.subject
Ligands
en
dc.subject
Animals
en
dc.subject
Immunological Synapses
en
dc.subject
Mice
en
dc.subject
Receptors
en
dc.subject
CD4-Positive T-Lymphocytes
en
dc.subject
Antigen
en
dc.subject
T-Cell
en
dc.title
CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions