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 language | English |
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Pages (from-to) | 2853-2861 |
Number of pages | 9 |
Journal | Journal of Immunology |
Volume | 170 |
Issue number | 6 |
DOIs | |
State | Published - 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