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

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 f...

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Hauptverfasser: Hoffmann, Sabrina (VerfasserIn) , Hadji Hosseini, Babak (VerfasserIn) , Hecker, Markus (VerfasserIn) , Louban, Ilia (VerfasserIn) , Bulbuc, Nadja (VerfasserIn) , Garbi, Natalio (VerfasserIn) , Wabnitz, Guido H. (VerfasserIn) , Samstag, Yvonne (VerfasserIn) , Spatz, Joachim P. (VerfasserIn) , Hämmerling, Günter J. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: [30 April 2011]
In: Immunology letters
Year: 2011, Jahrgang: 136, Heft: 1, Pages: 13-20
ISSN:1879-0542
DOI:10.1016/j.imlet.2010.11.005
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.imlet.2010.11.005
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0165247810002944
Volltext
Verfasserangaben:Sabrina Hoffmann, Babak H. Hosseini, Markus Hecker, Ilia Louban, Nadja Bulbuc, Natalio Garbi, Guido H. Wabnitz, Yvonne Samstag, Joachim P. Spatz, Günter J. Hämmerling

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520 |a 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. 
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