دورية أكاديمية
The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing.
العنوان: | The CD3 conformational change in the γδ T cell receptor is not triggered by antigens but can be enforced to enhance tumor killing. |
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المؤلفون: | Dopfer EP; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Schänzlestrasse 18, 79108 Freiburg, Germany; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79104 Freiburg, Germany., Hartl FA; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Schänzlestrasse 18, 79108 Freiburg, Germany; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79104 Freiburg, Germany., Oberg HH; Institute of Immunology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany., Siegers GM; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Schänzlestrasse 18, 79108 Freiburg, Germany; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79104 Freiburg, Germany; Robarts Research Institute, Department of Anatomy and Cell Biology, Robarts Research Institute, Western University, London, ON N6A 5B7, Canada., Yousefi OS; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Schänzlestrasse 18, 79108 Freiburg, Germany; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University Freiburg, 79104 Freiburg, Germany., Kock S; Institute of Pathology, University Medical Center Freiburg, 79106 Freiburg, Germany., Fiala GJ; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Schänzlestrasse 18, 79108 Freiburg, Germany; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University Freiburg, 79104 Freiburg, Germany., Garcillán B; Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain., Sandstrom A; Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637, USA., Alarcón B; Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autonoma de Madrid, 28049 Madrid, Spain., Regueiro JR; Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain., Kabelitz D; Institute of Immunology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany., Adams EJ; Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637, USA., Minguet S; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Schänzlestrasse 18, 79108 Freiburg, Germany; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79104 Freiburg, Germany., Wesch D; Institute of Immunology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany., Fisch P; Institute of Pathology, University Medical Center Freiburg, 79106 Freiburg, Germany., Schamel WWA; Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signaling Studies and Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Schänzlestrasse 18, 79108 Freiburg, Germany; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79104 Freiburg, Germany. Electronic address: wolfgang.schamel@biologie.uni-freiburg.de. |
المصدر: | Cell reports [Cell Rep] 2014 Jun 12; Vol. 7 (5), pp. 1704-1715. Date of Electronic Publication: 2014 May 22. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
مواضيع طبية MeSH: | Cytotoxicity, Immunologic*, CD3 Complex/*chemistry , Receptors, Antigen, T-Cell, gamma-delta/*chemistry, Animals ; CD3 Complex/immunology ; Cell Line ; Humans ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Protein Binding ; Protein Conformation ; Receptor-CD3 Complex, Antigen, T-Cell/chemistry ; Receptor-CD3 Complex, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; T-Lymphocytes/immunology |
مستخلص: | Activation of the T cell receptor (TCR) by antigen is the key step in adaptive immunity. In the αβTCR, antigen induces a conformational change at the CD3 subunits (CD3 CC) that is absolutely required for αβTCR activation. Here, we demonstrate that the CD3 CC is not induced by antigen stimulation of the mouse G8 or the human Vγ9Vδ2 γδTCR. We find that there is a fundamental difference between the activation mechanisms of the αβTCR and γδTCR that map to the constant regions of the TCRαβ/γδ heterodimers. Enforced induction of CD3 CC with a less commonly used monoclonal anti-CD3 promoted proximal γδTCR signaling but inhibited cytokine secretion. Utilizing this knowledge, we could dramatically improve in vitro tumor cell lysis by activated human γδ T cells. Thus, manipulation of the CD3 CC might be exploited to improve clinical γδ T cell-based immunotherapies. (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.) |
المشرفين على المادة: | 0 (CD3 Complex) 0 (Receptor-CD3 Complex, Antigen, T-Cell) 0 (Receptors, Antigen, T-Cell, gamma-delta) |
تواريخ الأحداث: | Date Created: 20140527 Date Completed: 20150821 Latest Revision: 20171116 |
رمز التحديث: | 20240628 |
DOI: | 10.1016/j.celrep.2014.04.049 |
PMID: | 24857663 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2211-1247 |
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DOI: | 10.1016/j.celrep.2014.04.049 |