Abstract
How Cbl family proteins regulate T cell responses is unclear. We found that c-Cbl Cbl-b double knock-out (dKO) T cells became hyperresponsive upon anti-CD3 stimulation, even though the major T cell antigen receptor (TCR) signaling pathways were not enhanced. The dKO T cells did not down-modulate surface TCR after ligand engagement, which resulted in sustained TCR signaling. However, these cells showed normal ligand-independent TCR internalization, and trafficking of internalized TCR to the lysosome compartment after ligand engagement was reduced. These findings show that Cbl family proteins negatively regulate T cell activation by promoting clearance of engaged TCR from the cell surface, a process that is apparently essential for the termination of TCR signals.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / immunology*
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Down-Regulation / immunology
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Ligands
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Phosphoproteins / genetics
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Phosphoproteins / immunology*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / immunology*
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Proto-Oncogene Proteins c-cbl
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Receptors, Antigen, T-Cell / immunology*
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocytes / immunology*
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Ubiquitin-Protein Ligases*
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Cblb protein, mouse
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Ligands
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Phosphoproteins
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Proto-Oncogene Proteins
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Receptors, Antigen, T-Cell
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Proto-Oncogene Proteins c-cbl
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Ubiquitin-Protein Ligases
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Cbl protein, mouse