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

التفاصيل البيبلوغرافية
العنوان: Optogenetic control shows that kinetic proofreading regulates the activity of the T cell receptor.
المؤلفون: Yousefi OS; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg, Germany., Günther M; Division of Theoretical Systems Biology, German Cancer Research Center, Heidelberg, Germany.; BioQuant Center, University of Heidelberg, Heidelberg, Germany., Hörner M; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany., Chalupsky J; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency, Medical Center Freiburg and Faculty of Medicine, University of Freiburg, Freiburg, Germany., Wess M; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany., Brandl SM; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany., Smith RW; Laboratory of Systems and Synthetic Biology, Wageningen University and Research, Wageningen, Netherlands., Fleck C; Laboratory of Systems and Synthetic Biology, Wageningen University and Research, Wageningen, Netherlands., Kunkel T; Faculty of Biology, University of Freiburg, Freiburg, Germany., Zurbriggen MD; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; Institute of Synthetic Biology and Cluster of Excellence on Plant Sciences, University of Düsseldorf, Düsseldorf, Germany., Höfer T; Division of Theoretical Systems Biology, German Cancer Research Center, Heidelberg, Germany.; BioQuant Center, University of Heidelberg, Heidelberg, Germany., Weber W; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany., Schamel WW; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; Laboratory of Systems and Synthetic Biology, Wageningen University and Research, Wageningen, Netherlands.
المصدر: ELife [Elife] 2019 Apr 05; Vol. 8. Date of Electronic Publication: 2019 Apr 05.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Signal Transduction*, Antigens/*metabolism , Phytochrome B/*metabolism , Receptors, Antigen, T-Cell/*metabolism , T-Lymphocytes/*immunology, Humans ; Jurkat Cells ; Kinetics ; Light ; Models, Theoretical ; Optogenetics/methods ; Protein Binding
مستخلص: 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.
Competing Interests: OY, MG, MH, JC, MW, SB, RS, CF, TK, MZ, TH, WW, WS No competing interests declared
(© 2019, Yousefi et al.)
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معلومات مُعتمدة: EXC2189 International Deutsche Forschungsgemeinschaft; GSC-4 International Deutsche Forschungsgemeinschaft; EXC294 International Deutsche Forschungsgemeinschaft; EXC81 International Deutsche Forschungsgemeinschaft; INST 39/899-1 FUGG International Deutsche Forschungsgemeinschaft
فهرسة مساهمة: Keywords: A. thaliana; T cells; dynamics; human; immunology; inflammation; ligand-receptor; optogenetics; signaling
المشرفين على المادة: 0 (Antigens)
0 (Receptors, Antigen, T-Cell)
136250-22-1 (Phytochrome B)
تواريخ الأحداث: Date Created: 20190406 Date Completed: 20200228 Latest Revision: 20200309
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6488296
DOI: 10.7554/eLife.42475
PMID: 30947807
قاعدة البيانات: MEDLINE
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