Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation

Cell. 2002 Jun 28;109(7):901-12. doi: 10.1016/s0092-8674(02)00799-7.

Abstract

How membrane receptors initiate signal transduction upon ligand binding is a matter of intense scrutiny. The T cell receptor complex (TCR-CD3) is composed of TCR alpha/beta ligand binding subunits bound to the CD3 subunits responsible for signal transduction. Although it has long been speculated that TCR-CD3 may undergo a conformational change, confirmation is still lacking. We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3 epsilon and results in recruitment of the adaptor protein Nck. This occurs earlier than and independently of tyrosine kinase activation. Finally, by interfering with Nck-CD3 epsilon association in vivo, we demonstrate that TCR-CD3 recruitment of Nck is critical for maturation of the immune synapse and for T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Binding Sites
  • CD3 Complex*
  • Humans
  • Jurkat Cells
  • Ligands
  • Lymphocyte Activation
  • Mice
  • Molecular Sequence Data
  • Oncogene Proteins / chemistry
  • Oncogene Proteins / metabolism*
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Proline / metabolism
  • Protein Binding
  • Receptors, Antigen, T-Cell / chemistry*
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • src Homology Domains

Substances

  • Adaptor Proteins, Signal Transducing
  • CD3 Complex
  • CD3E protein, human
  • Ligands
  • Nck protein
  • Oncogene Proteins
  • Receptors, Antigen, T-Cell
  • Phosphotyrosine
  • Proline