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

O.S. 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 W.A. Schamel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

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.

Original languageEnglish
JournaleLife
Volume8
DOIs
Publication statusPublished - 5 Apr 2019

Fingerprint

Optogenetics
T-Cell Antigen Receptor
Ligands
Kinetics
Phytochrome B
Light
Plant Photoreceptors
T-cells
Immune system
Autoantigens
Cell Communication
Half-Life
Immune System
T-Lymphocytes

Keywords

  • A. thaliana
  • dynamics
  • human
  • immunology
  • inflammation
  • ligand-receptor
  • optogenetics
  • signaling
  • T cells

Cite this

Yousefi, O. S., Günther, M., Hörner, M., Chalupsky, J., Wess, M., Brandl, S. M., ... Schamel, W. W. A. (2019). Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor. eLife, 8. https://doi.org/10.7554/eLife.42475
Yousefi, O.S. ; Günther, Matthias ; Hörner, Maximilian ; Chalupsky, Julia ; Wess, Maximilian ; Brandl, Simon M. ; Smith, Robert W. ; Fleck, Christian ; Kunkel, Tim ; Zurbriggen, Matias D. ; Höfer, Thomas ; Weber, Wilfried ; Schamel, Wolfgang W.A. / Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor. In: eLife. 2019 ; Vol. 8.
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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.",
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Yousefi, OS, Günther, M, Hörner, M, Chalupsky, J, Wess, M, Brandl, SM, Smith, RW, Fleck, C, Kunkel, T, Zurbriggen, MD, Höfer, T, Weber, W & Schamel, WWA 2019, 'Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor', eLife, vol. 8. https://doi.org/10.7554/eLife.42475

Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor. / Yousefi, O.S.; Günther, Matthias; Hörner, Maximilian; Chalupsky, Julia; Wess, Maximilian; Brandl, Simon M.; Smith, Robert W.; Fleck, Christian; Kunkel, Tim; Zurbriggen, Matias D.; Höfer, Thomas; Weber, Wilfried; Schamel, Wolfgang W.A.

In: eLife, Vol. 8, 05.04.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor

AU - Yousefi, O.S.

AU - Günther, Matthias

AU - Hörner, Maximilian

AU - Chalupsky, Julia

AU - Wess, Maximilian

AU - Brandl, Simon M.

AU - Smith, Robert W.

AU - Fleck, Christian

AU - Kunkel, Tim

AU - Zurbriggen, Matias D.

AU - Höfer, Thomas

AU - Weber, Wilfried

AU - Schamel, Wolfgang W.A.

PY - 2019/4/5

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AB - 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.

KW - A. thaliana

KW - dynamics

KW - human

KW - immunology

KW - inflammation

KW - ligand-receptor

KW - optogenetics

KW - signaling

KW - T cells

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SN - 2050-084X

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