دورية أكاديمية
Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding.
العنوان: | Cross-TCR Antagonism Revealed by Optogenetically Tuning the Half-Life of the TCR Ligand Binding. |
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المؤلفون: | Yousefi OS; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, 79104 Freiburg, Germany.; Center of Chronic Immunodeficiency CCI, University Clinics and Medical Faculty, 79110 Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University Freiburg, 79104 Freiburg, Germany., Ruggieri M; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, 79104 Freiburg, Germany.; Center of Chronic Immunodeficiency CCI, University Clinics and Medical Faculty, 79110 Freiburg, Germany.; Department of Pathology, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany., Idstein V; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, 79104 Freiburg, Germany.; Center of Chronic Immunodeficiency CCI, University Clinics and Medical Faculty, 79110 Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University Freiburg, 79104 Freiburg, Germany., von Prillwitz KU; Institute of Physics, University of Freiburg, 79104 Freiburg, Germany.; Freiburg Center for Data Analysis and Modeling (FDM), University of Freiburg, 79104 Freiburg, Germany., Herr LA; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, 79104 Freiburg, Germany.; Center of Chronic Immunodeficiency CCI, University Clinics and Medical Faculty, 79110 Freiburg, Germany., Chalupsky J; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, 79104 Freiburg, Germany.; Center of Chronic Immunodeficiency CCI, University Clinics and Medical Faculty, 79110 Freiburg, Germany., Köhn M; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, 79104 Freiburg, Germany., Weber W; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, 79104 Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University Freiburg, 79104 Freiburg, Germany., Timmer J; Signalling Research Centres BIOSS and CIBSS, 79104 Freiburg, Germany.; Institute of Physics, University of Freiburg, 79104 Freiburg, Germany.; Freiburg Center for Data Analysis and Modeling (FDM), University of Freiburg, 79104 Freiburg, Germany., Schamel WWA; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, 79104 Freiburg, Germany.; Center of Chronic Immunodeficiency CCI, University Clinics and Medical Faculty, 79110 Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University Freiburg, 79104 Freiburg, Germany. |
المصدر: | International journal of molecular sciences [Int J Mol Sci] 2021 May 06; Vol. 22 (9). Date of Electronic Publication: 2021 May 06. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
مواضيع طبية MeSH: | Optogenetics*, Receptors, Antigen, T-Cell/*antagonists & inhibitors, Antibodies/metabolism ; Cell Membrane/metabolism ; Green Fluorescent Proteins/metabolism ; HEK293 Cells ; Half-Life ; Humans ; Jurkat Cells ; Ligands ; Models, Biological ; Receptors, Antigen, T-Cell/metabolism |
مستخلص: | 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. |
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معلومات مُعتمدة: | EXC294 Deutsche Forschungsgemeinschaft; EXC 2189 Deutsche Forschungsgemeinschaft; SFB854 Deutsche Forschungsgemeinschaft; SFB1381 Deutsche Forschungsgemeinschaft; GSC-4 Deutsche Forschungsgemeinschaft |
فهرسة مساهمة: | Keywords: T cell activation; TCR; antagonism; modeling; signaling; synthetic biology |
المشرفين على المادة: | 0 (Antibodies) 0 (Ligands) 0 (Receptors, Antigen, T-Cell) 147336-22-9 (Green Fluorescent Proteins) |
تواريخ الأحداث: | Date Created: 20210602 Date Completed: 20210622 Latest Revision: 20210622 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC8124730 |
DOI: | 10.3390/ijms22094920 |
PMID: | 34066527 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1422-0067 |
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DOI: | 10.3390/ijms22094920 |