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Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor

Author

Listed:
  • Javier Casas

    (Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
    The Scripps Research Institute)

  • Joanna Brzostek

    (Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
    The Scripps Research Institute)

  • Veronika I. Zarnitsyna

    (Georgia Institute of Technology and Emory University
    Present address: Department of Biology, Emory University, Atlanta, Georgia 30332, USA)

  • Jin-sung Hong

    (George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology and Emory University)

  • Qianru Wei

    (Yong Loo Lin School of Medicine, National University Health System, National University of Singapore)

  • John A. H. Hoerter

    (The Scripps Research Institute
    Present address: Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA)

  • Guo Fu

    (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)

  • Jeanette Ampudia

    (The Scripps Research Institute
    Present address: Takeda Pharmaceutical Company, San Diego, California 92121, USA)

  • Rose Zamoyska

    (Institute of Immunology and Infection Research, University of Edinburgh)

  • Cheng Zhu

    (Georgia Institute of Technology and Emory University
    George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology and Emory University)

  • Nicholas R. J. Gascoigne

    (Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
    The Scripps Research Institute)

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.

Suggested Citation

  • Javier Casas & Joanna Brzostek & Veronika I. Zarnitsyna & Jin-sung Hong & Qianru Wei & John A. H. Hoerter & Guo Fu & Jeanette Ampudia & Rose Zamoyska & Cheng Zhu & Nicholas R. J. Gascoigne, 2014. "Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6624
    DOI: 10.1038/ncomms6624
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    Cited by:

    1. Muaz Nik Rushdi & Victor Pan & Kaitao Li & Hyun-Kyu Choi & Stefano Travaglino & Jinsung Hong & Fletcher Griffitts & Pragati Agnihotri & Roy A. Mariuzza & Yonggang Ke & Cheng Zhu, 2022. "Cooperative binding of T cell receptor and CD4 to peptide-MHC enhances antigen sensitivity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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