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 TCR alpha subunit restores development of pT alpha-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 alpha beta TCR 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 Ca(2+) 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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Enzyme Activation / immunology
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Ligands
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Lymphocyte Activation* / genetics
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology
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Membrane Microdomains / immunology
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Membrane Microdomains / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, SCID
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Mice, Transgenic
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Mitogen-Activated Protein Kinases / metabolism
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Organ Culture Techniques
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Receptors, Antigen, T-Cell, alpha-beta / deficiency
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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Receptors, Antigen, T-Cell, alpha-beta / physiology
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Stem Cells / enzymology
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Stem Cells / immunology*
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Stem Cells / metabolism*
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T-Lymphocyte Subsets / enzymology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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Thymus Gland / cytology
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Thymus Gland / enzymology
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Thymus Gland / immunology
Substances
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Ligands
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Membrane Glycoproteins
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Receptors, Antigen, T-Cell, alpha-beta
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pre-T cell receptor alpha
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Mitogen-Activated Protein Kinases