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| Item Type: | Article |
|---|---|
| Title: | CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions |
| Creators Name: | Schrangl, Lukas, Kellner, Florian, Platzer, René, Mühlgrabner, Vanessa, Hubinger, Paul, Wieland, Josephine, Obst, Reinhard, Toca-Herrera, José L., Huppa, Johannes B., Schütz, Gerhard J. and Göhring, Janett |
| 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. |
| Keywords: | Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 16 |
| Number: | 1 |
| Page Range: | 7577 |
| Date: | 15 August 2025 |
| Official Publication: | https://doi.org/10.1038/s41467-025-62104-2 |
| PubMed: | View item in PubMed |
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