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Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor

The immune system distinguishes between self and foreign antigens. The kinetic proofreading (KPR) model proposes that T cells discriminate self from foreign ligands by the different ligand binding half-lives to the T cell receptor (TCR). It is challenging to test KPR as the available experimental sy...

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Hauptverfasser: Yousefi, Omid Sascha (VerfasserIn) , Günther, Matthias (VerfasserIn) , Höfer, Thomas (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 05 April 2019
In: eLife
Year: 2019, Jahrgang: 8
ISSN:2050-084X
DOI:10.7554/eLife.42475
Online-Zugang:Verlag, Volltext: https://doi.org/10.7554/eLife.42475
Volltext
Verfasserangaben:O Sascha Yousefi, Matthias Günther, Maximilian Hörner, Julia Chalupsky, Maximilian Wess, Simon M Brandl, Robert W Smith, Christian Fleck, Tim Kunkel, Matias D Zurbriggen, Thomas Höfer, Wilfried Weber, Wolfgang WA Schamel
Beschreibung
Zusammenfassung:The immune system distinguishes between self and foreign antigens. The kinetic proofreading (KPR) model proposes that T cells discriminate self from foreign ligands by the different ligand binding half-lives to the T cell receptor (TCR). It is challenging to test KPR as the available experimental systems fall short of only altering the binding half-lives and keeping other parameters of the interaction unchanged. We engineered an optogenetic system using the plant photoreceptor phytochrome B (PhyB) as a ligand to selectively control the dynamics of ligand binding to the TCR by light. This opto-ligand-TCR system was combined with the unique property of PhyB to continuously cycle between the binding and non-binding states under red light, with the light intensity determining the cycling rate and thus the binding duration. Mathematical modeling of our experimental datasets showed that indeed the ligand-TCR interaction half-life is the decisive factor for activating downstream TCR signaling, substantiating KPR.
Beschreibung:Gesehen am 23.07.2019
Beschreibung:Online Resource
ISSN:2050-084X
DOI:10.7554/eLife.42475

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