Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor
- University of Freiburg, Germany
- German Cancer Research Center (DKFZ), Germany
- Wageningen UR, Netherlands
Abstract
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.
Data availability
All data that were analyzed with the mathematical model are provided in source data files.
Article and author information
Author details
Wolfgang WA Schamel
Funding
Deutsche Forschungsgemeinschaft (GSC-4)
- O Sascha Yousefi
- Maximilian Hörner
Deutsche Forschungsgemeinschaft (EXC294)
- Wolfgang WA Schamel
Deutsche Forschungsgemeinschaft (EXC81)
- Thomas Höfer
Deutsche Forschungsgemeinschaft (EXC2189)
- Wolfgang WA Schamel
Deutsche Forschungsgemeinschaft (INST 39/899-1 FUGG)
- Wolfgang WA Schamel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Arup K Chakraborty, Massachusetts Institute of Technology, United States
Version history
- Received: October 2, 2018
- Accepted: March 5, 2019
- Accepted Manuscript published: April 5, 2019 (version 1)
- Version of Record published: April 29, 2019 (version 2)
Copyright
© 2019, Yousefi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor
eLife 8:e42475.
https://doi.org/10.7554/eLife.42475
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