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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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
05 April 2019
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| In: |
eLife
Year: 2019, Volume: 8 |
| ISSN: | 2050-084X |
| DOI: | 10.7554/eLife.42475 |
| Online Access: | Verlag, Volltext: https://doi.org/10.7554/eLife.42475
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 23.07.2019 |
| Physical Description: | Online Resource |
| ISSN: | 2050-084X |
| DOI: | 10.7554/eLife.42475 |