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Author Notes:

Correspondence should be addressed to N.R.J.G. (micnrjg@nus.edu.sg).

We thank Kersi Pestonjamasp for technical help, Lorena García and Joaquín Sebastián for their critical reading and the NIH Tetramer Core Facility for production of biotinylated MHCI proteins and tetramers.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences, the National Institutes of Health, or other funding agencies.

This is manuscript number 27062 from The Scripps Research Institute.

J.C. performed most of the experiments. J.B., J.A.H.H., G.F, Q.W. and J.A. generated antigen presenting cell lines, constructs and mutants.

V.Z. and J.H. performed adhesion frequency assays.

J.C., J.B., V.Z., and J.H. analyzed data; J.C. and N.R.J.G. designed the project with help and insight from J.C., J.B. and C.Z.; J.C. and N.R.J.G. wrote the manuscript.

The authors declare no competing financial interests.

Subjects:

Research Funding:

Supported by National University of Singapore and NIH grants GM065230 to N.R.J.G. and GM96187 and AI038282 to C.Z.

J.A.H.H. was supported by NIH training grant T32AI07244.

R.Z. is supported by Investigator Award 096669 from the Wellcome Trust.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • T-CELL-ACTIVATION
  • SRC-FAMILY KINASES
  • MHC CLASS-I
  • IMMUNOLOGICAL SYNAPSE
  • TYROSINE PHOSPHORYLATION
  • RECEPTOR INTERACTION
  • DIFFERENTIATION
  • P56(LCK)
  • COMPLEX
  • FRET

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

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Journal Title:

Nature Communications

Volume:

Volume 5

Publisher:

, Pages 5624-5624

Type of Work:

Article | Post-print: After Peer Review

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.

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© 2014 Macmillan Publishers Limited. All rights reserved.

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