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Medientyp:
E-Artikel
Titel:
Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding
Beteiligte:
Yousefi, Omid Sascha;
Ruggieri, Matias;
Idstein, Vincent;
von Prillwitz, Kai Uwe;
Herr, Laurenz A.;
Chalupsky, Julia;
Köhn, Maja;
Weber, Wilfried;
Timmer, Jens;
Schamel, Wolfgang W. A.
Erschienen:
MDPI AG, 2021
Erschienen in:
International Journal of Molecular Sciences, 22 (2021) 9, Seite 4920
Sprache:
Englisch
DOI:
10.3390/ijms22094920
ISSN:
1422-0067
Entstehung:
Anmerkungen:
Beschreibung:
Activation of T cells by agonistic peptide-MHC can be inhibited by antagonistic ones. However, the exact mechanism remains elusive. We used Jurkat cells expressing two different TCRs and tested whether stimulation of the endogenous TCR by agonistic anti-Vβ8 antibodies can be modulated by ligand-binding to the second, optogenetic TCR. The latter TCR uses phytochrome B tetramers (PhyBt) as ligand, the binding half-life of which can be altered by light. We show that this half-life determined whether the PhyBt acted as a second agonist (long half-life), an antagonist (short half-life) or did not have any influence (very short half-life) on calcium influx. A mathematical model of this cross-antagonism shows that a mechanism based on an inhibitory signal generated by early recruitment of a phosphatase and an activating signal by later recruitment of a kinase explains the data.