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

• Type of Material: Article
• Authors: Javier Casas, National University of Singapore; Joanna Brzostek, National University of Singapore; Veronika Zarnitsyna, Emory University; Jin-sung Hong, Emory University; Qianru Wei, National University of Singapore; John A. H. Hoerter, Scripps Research Institute; Guo Fu, Scripps Research Institute; Jeanette Ampudia, Scripps Research Institute; Rose Zamoyska, University of Edinburgh; Cheng Zhu, Emory University; Nicholas R. J. Gascoigne, National University of Singapore
• Language: English
• Date: 2014-11-01
• Publisher: Nature Publishing Group: Nature Communications
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Macmillan Publishers Limited. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/ncomms6624
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 5
• Start Page: 5624
• End Page: 5624
• Grant/Funding Information: J.A.H.H. was supported by NIH training grant T32AI07244.; Supported by National University of Singapore and NIH grants GM065230 to N.R.J.G. and GM96187 and AI038282 to C.Z.; R.Z. is supported by Investigator Award 096669 from the Wellcome Trust.
• Keywords: IMMUNOLOGICAL SYNAPSE; TYROSINE PHOSPHORYLATION; FRET; P56(LCK); Multidisciplinary Sciences; Science & Technology; SRC-FAMILY KINASES; T-CELL-ACTIVATION; MHC CLASS-I; RECEPTOR INTERACTION; DIFFERENTIATION; COMPLEX; Science & Technology - Other Topics
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

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.