Low activation threshold as a mechanism for ligand-independent signaling in pre-T cells

Mariëlle C. Haks, Stanley M. Belkowski, Maria Ciofani, Michele Rhodes, Juliette M. Lefebvre, Sebastién Trop, Patrice Hugo, Juan Carlos Zúñiga-Pflücker, David L. Wiest

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Pre-TCR complexes are thought to signal in a ligand-independent manner because they are constitutively targeted to lipid rafts. We report that ligand-independent signaling is not a unique capability of the pre-TCR complex. Indeed, the TCRα subunit restores development of pTα-deficient thymocytes to the CD4+CD8+ stage even in the absence of conventional MHC class I and class II ligands. Moreover, we found that pre-TCR and αβTCR complexes exhibit no appreciable difference in their association with lipid rafts, suggesting that ligand-independence is a function of the CD4-CD8- (DN) thymocytes in which pre-TCR signaling occurs. In agreement, we found that only CD44-CD25+ DN thymocytes (DN3) enabled activation of extracellular signal-regulated kinases by the pre-TCR complex. DN thymocytes also exhibited a lower signaling threshold relative to CD4+CD8+ thymocytes, which was associated with both the markedly elevated lipid raft content of their plasma membranes and more robust capacitative Ca2+ entry. Taken together these data suggest that cell-autonomous, ligand-independent signaling is primarily a property of the thymocytes in which pre-TCR signaling occurs.

Original languageEnglish
Pages (from-to)2853-2861
Number of pages9
JournalJournal of Immunology
Volume170
Issue number6
DOIs
StatePublished - Mar 15 2003

Keywords

  • Animals
  • Cell Differentiation/genetics
  • Enzyme Activation/immunology
  • Ligands
  • Lymphocyte Activation/genetics
  • Membrane Glycoproteins/deficiency
  • Membrane Microdomains/immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinases/metabolism
  • Organ Culture Techniques
  • Receptors, Antigen, T-Cell, alpha-beta/deficiency
  • Signal Transduction/genetics
  • Stem Cells/enzymology
  • T-Lymphocyte Subsets/enzymology
  • Thymus Gland/cytology

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