Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor
The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction b...
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Published in | Nature communications Vol. 5; no. 1; p. 5624 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
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London
Nature Publishing Group UK
27.11.2014
Nature Publishing Group |
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Online Access | Get full text |
ISSN | 2041-1723 2041-1723 |
DOI | 10.1038/ncomms6624 |
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Abstract | The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ–CD8 interactions require CD8–MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck.
The early signalling events that trigger initial T-cell receptor signalling are not clearly defined. Here the authors show that this occurs in two stages, the first between the CD8 coreceptor and CD3 requiring Lck association to CD8, while the second interaction requires binding of major histocompatibility molecules. |
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AbstractList | The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ-CD8 interactions require CD8-MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck. The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ–CD8 interactions require CD8–MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck. The early signalling events that trigger initial T-cell receptor signalling are not clearly defined. Here the authors show that this occurs in two stages, the first between the CD8 coreceptor and CD3 requiring Lck association to CD8, while the second interaction requires binding of major histocompatibility molecules. The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ-CD8 interactions require CD8-MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck.The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ-CD8 interactions require CD8-MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck. The earliest molecular events in T cell recognition have not yet been fully described, and the initial T cell receptor (TCR) triggering mechanism remains a subject of controversy. Here, using TIRF/FRET microscopy, we observe a two-stage interaction between TCR, CD8, and MHCp. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ-CD8 interactions require CD8-MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR triggering event is induced by free Lck. |
ArticleNumber | 5624 |
Author | Gascoigne, Nicholas R. J. Zarnitsyna, Veronika I. Zamoyska, Rose Brzostek, Joanna Hoerter, John A. H. Fu, Guo Zhu, Cheng Casas, Javier Wei, Qianru Hong, Jin-sung Ampudia, Jeanette |
AuthorAffiliation | 1 Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 5 Science Drive 2, Singapore 117545 2 Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA, 92037 USA 3 Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA 4 George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA 5 Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, Scotland, UK |
AuthorAffiliation_xml | – name: 1 Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 5 Science Drive 2, Singapore 117545 – name: 5 Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, Scotland, UK – name: 3 Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA – name: 2 Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA, 92037 USA – name: 4 George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA |
Author_xml | – sequence: 1 givenname: Javier surname: Casas fullname: Casas, Javier organization: Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Department of Immunology and Microbial Sciences, The Scripps Research Institute – sequence: 2 givenname: Joanna surname: Brzostek fullname: Brzostek, Joanna organization: Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Department of Immunology and Microbial Sciences, The Scripps Research Institute – sequence: 3 givenname: Veronika I. surname: Zarnitsyna fullname: Zarnitsyna, Veronika I. organization: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Present address: Department of Biology, Emory University, Atlanta, Georgia 30332, USA – sequence: 4 givenname: Jin-sung surname: Hong fullname: Hong, Jin-sung organization: George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology and Emory University – sequence: 5 givenname: Qianru surname: Wei fullname: Wei, Qianru organization: Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore – sequence: 6 givenname: John A. H. surname: Hoerter fullname: Hoerter, John A. H. organization: Department of Immunology and Microbial Sciences, The Scripps Research Institute, Present address: Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA – sequence: 7 givenname: Guo surname: Fu fullname: Fu, Guo organization: Department of Immunology and Microbial Sciences, The Scripps Research Institute, Present address: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Fujian 361102, China – sequence: 8 givenname: Jeanette surname: Ampudia fullname: Ampudia, Jeanette organization: Department of Immunology and Microbial Sciences, The Scripps Research Institute, Present address: Takeda Pharmaceutical Company, San Diego, California 92121, USA – sequence: 9 givenname: Rose surname: Zamoyska fullname: Zamoyska, Rose organization: Institute of Immunology and Infection Research, University of Edinburgh – sequence: 10 givenname: Cheng surname: Zhu fullname: Zhu, Cheng organization: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology and Emory University – sequence: 11 givenname: Nicholas R. J. surname: Gascoigne fullname: Gascoigne, Nicholas R. J. email: micnrjg@nus.edu.sg organization: Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Department of Immunology and Microbial Sciences, The Scripps Research Institute |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-2 content type line 23 Present addresses: V.I.Z., Department of Biology, Emory University, Atlanta, GA; J.A.H.H., Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA; G.F., State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Fujian 361102, China; J.A., Takeda Pharmaceutical Company, San Diego, CA 92121, USA. |
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Snippet | The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a... The earliest molecular events in T cell recognition have not yet been fully described, and the initial T cell receptor (TCR) triggering mechanism remains a... |
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SubjectTerms | 13/109 13/95 14/33 14/35 14/63 631/250/1619/554/1775 631/250/21/324 82/29 82/83 96/31 96/33 96/35 Animals CD3 Complex - genetics CD3 Complex - metabolism CD8 Antigens - genetics CD8 Antigens - metabolism Energy transfer Female Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humanities and Social Sciences Ligands Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - genetics Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism Major Histocompatibility Complex Male Mice Mice, Knockout multidisciplinary Protein Binding Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - metabolism Science Science (multidisciplinary) Synapses - enzymology Synapses - genetics Synapses - metabolism T-Lymphocytes - metabolism |
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Title | Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor |
URI | https://link.springer.com/article/10.1038/ncomms6624 https://www.ncbi.nlm.nih.gov/pubmed/25427562 https://www.proquest.com/docview/1628243941 https://www.proquest.com/docview/1628881161 https://pubmed.ncbi.nlm.nih.gov/PMC4248239 |
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