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

Javier Casas, Joanna Brzostek, Veronika I. Zarnitsyna, Jin-sung Hong, Qianru Wei, John A. H. Hoerter, Guo Fu, Jeanette Ampudia, Rose Zamoyska, Cheng Zhu and Nicholas R. J. Gascoigne ()
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Javier Casas: Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
Joanna Brzostek: Yong Loo Lin School of Medicine, National University Health System, National University of Singapore
Veronika I. Zarnitsyna: Georgia Institute of Technology and Emory University
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
Guo Fu: The Scripps Research Institute
Jeanette Ampudia: The Scripps Research Institute
Rose Zamoyska: Institute of Immunology and Infection Research, University of Edinburgh
Cheng Zhu: 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

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6624

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