Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding
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-bind...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/9/4920 |
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| author | Omid Sascha Yousefi Matias Ruggieri Vincent Idstein Kai Uwe von Prillwitz Laurenz A. Herr Julia Chalupsky Maja Köhn Wilfried Weber Jens Timmer Wolfgang W. A. Schamel |
| author_facet | Omid Sascha Yousefi Matias Ruggieri Vincent Idstein Kai Uwe von Prillwitz Laurenz A. Herr Julia Chalupsky Maja Köhn Wilfried Weber Jens Timmer Wolfgang W. A. Schamel |
| author_sort | Omid Sascha Yousefi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:39:44Z |
| format | Article |
| id | doaj.art-3258b2875f984b4c8bb0c4ded395fa65 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:39:44Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3258b2875f984b4c8bb0c4ded395fa652023-11-21T18:34:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01229492010.3390/ijms22094920Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand BindingOmid Sascha Yousefi0Matias Ruggieri1Vincent Idstein2Kai Uwe von Prillwitz3Laurenz A. Herr4Julia Chalupsky5Maja Köhn6Wilfried Weber7Jens Timmer8Wolfgang W. A. Schamel9Faculty of Biology, University of Freiburg, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyInstitute of Physics, University of Freiburg, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanySignalling Research Centres BIOSS and CIBSS, 79104 Freiburg, GermanyFaculty of Biology, University of Freiburg, 79104 Freiburg, GermanyActivation 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.https://www.mdpi.com/1422-0067/22/9/4920antagonismsignalingTCRT cell activationmodelingsynthetic biology |
| spellingShingle | Omid Sascha Yousefi Matias Ruggieri Vincent Idstein Kai Uwe von Prillwitz Laurenz A. Herr Julia Chalupsky Maja Köhn Wilfried Weber Jens Timmer Wolfgang W. A. Schamel Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding International Journal of Molecular Sciences antagonism signaling TCR T cell activation modeling synthetic biology |
| title | Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding |
| title_full | Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding |
| title_fullStr | Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding |
| title_full_unstemmed | Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding |
| title_short | Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding |
| title_sort | cross tcr antagonism revealed by optogenetically tuning the half life of the tcr ligand binding |
| topic | antagonism signaling TCR T cell activation modeling synthetic biology |
| url | https://www.mdpi.com/1422-0067/22/9/4920 |
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