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| Item Type: | Article |
|---|---|
| Title: | Temporal analysis of T-cell receptor-imposed forces via quantitative single molecule FRET measurements |
| Creators Name: | Göhring, J., Kellner, F., Schrangl, L., Platzer, R., Klotzsch, E., Stockinger, H., Huppa, J.B. and Schütz, G.J. |
| Abstract: | Mechanical forces acting on ligand-engaged T-cell receptors (TCRs) have previously been implicated in T-cell antigen recognition, yet their magnitude, spread, and temporal behavior are still poorly defined. We here report a FRET-based sensor equipped either with a TCR-reactive single chain antibody fragment or peptide-loaded MHC, the physiological TCR-ligand. The sensor was tethered to planar glass-supported lipid bilayers (SLBs) and informed most directly on the magnitude and kinetics of TCR-imposed forces at the single molecule level. When confronting T-cells with gel-phase SLBs we observed both prior and upon T-cell activation a single, well-resolvable force-peak of approximately 5 pN and force loading rates on the TCR of 1.5 pN per second. When facing fluid-phase SLBs instead, T-cells still exerted tensile forces yet of threefold reduced magnitude and only prior to but not upon activation. |
| Keywords: | CD4-Positive T-Lymphocytes, Cytochromes c, Fluorescence Resonance Energy Transfer, Histocompatibility Antigens, Kinetics, Ligands, Lipid Bilayers, Peptides, T-Cell Antigen Receptors, Single Molecule Imaging, Single-Chain Antibodies, Spatio-Temporal Analysis, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 12 |
| Number: | 1 |
| Page Range: | 2502 |
| Date: | 4 May 2021 |
| Official Publication: | https://doi.org/10.1038/s41467-021-22775-z |
| PubMed: | View item in PubMed |
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