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

Nat Commun. 2014 Nov 27;5:5624. doi: 10.1038/ncomms6624.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / genetics
  • CD3 Complex / metabolism*
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism*
  • Female
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Ligands
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism*
  • Major Histocompatibility Complex
  • Male
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Synapses / enzymology
  • Synapses / genetics
  • Synapses / metabolism
  • T-Lymphocytes / metabolism


  • CD3 Complex
  • CD3 antigen, zeta chain
  • CD8 Antigens
  • Homeodomain Proteins
  • Ligands
  • Receptors, Antigen, T-Cell
  • RAG-1 protein
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)