Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development

Nat Immunol. 2006 Jan;7(1):67-75. doi: 10.1038/ni1290. Epub 2005 Dec 4.


The pre-T cell receptor (TCR) is crucial for early T cell development and is proposed to function in a ligand-independent way. However, the molecular mechanism underlying the autonomous signals remains elusive. Here we show that the pre-TCR complex spontaneously formed oligomers. Specific charged residues in the extracellular domain of the pre-TCR alpha-chain mediated formation of the oligomers in vitro. Alteration of these residues eliminated the ability of the pre-TCR alpha-chain to support pre-TCR signaling in vivo. Dimerization but not raft localization of CD3epsilon was sufficient to simulate pre-TCR function and promote beta-selection. These results suggest that the pre-TCR complex can deliver its signal autonomously through oligomerization of the pre-TCR alpha-chain mediated by charged residues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / immunology*
  • Hematopoietic Stem Cells / cytology*
  • Humans
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Signal Transduction / immunology*
  • T-Lymphocytes / cytology*


  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • pre-T cell receptor alpha