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Single cell force spectroscopy of T cells recognizing a myelin-derived peptide on antigen presenting cells

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Hoffmann,  Sabrina
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

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Hosseini,  Babak H.
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

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Louban,  Ilia
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

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Spatz,  Joachim P.
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;

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Citation

Hoffmann, S., Hosseini, B. H., Hecker, M., Louban, I., Bulbuc, N., Garbi, N., et al. (2011). Single cell force spectroscopy of T cells recognizing a myelin-derived peptide on antigen presenting cells. Immunology Letters, 136(1), 13-20. doi:10.1016/j.imlet.2010.11.005.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-4DA8-7
Abstract
T-cell recognition of peptide-MHC complexes on APCs requires cell-cell interactions. The molecular events leading to T-cell activation have been extensively investigated, but the underlying physical binding forces between T-cells and APCs are largely unknown. We used single cell force spectroscopy for quantitation of interaction forces between T-cells and APCs presenting a tolerogenic peptide derived from myelin basic protein. When T-cells were brought into contact with peptide-loaded APCs, interaction forces increased with time from about 0.5nN after 10s interaction to about 15nN after 30min. In the absence of antigen, or when ICAM-1-negative APC was used, no increase in binding forces was observed. The temporal development of interaction forces correlated with the kinetics of immune synapse formation, as determined by LFA-1 and TCR enrichment at the interface of T-cell/APC conjugates using high throughput multispectral imaging flow cytometry. Together, these results suggest that ICAM-1/LFA-1 redistribution to the contact area is mainly responsible for development of strong interaction forces. High forces will keep T-cells and APCs in tight contact, thereby providing a platform for optimal interaction between TCRs and peptide-MHC complexes.