Abstract
T cell receptor (TCR) down-regulation is a consequence of specific receptor engagement and plays an important role in modulating the T cell response. We have investigated the role of protein kinase C (PKC) and protein tyrosine kinases (PTK) in the induction of TCR down-regulation. We report that the mutation of S126 in the CD3-gamma chain that is known to inhibit phorbol-12-myristate 13-acetate-induced TCR down-regulation does not affect down-regulation induced by a specific agonist. In addition, agonist-induced TCR down-regulation is not affected by blockade or depletion of PKC, neither by blockade or lack of PTK, while the same treatments efficiently interfere with T cell activation. These results demonstrate that TCR down-regulation is induced by early events which follow specific engagement by an agonist and can be dissociated from those required for full T cell activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CD3 Complex / physiology
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Down-Regulation / drug effects
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Down-Regulation / immunology*
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Enzyme Activation / drug effects
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Enzyme Activation / immunology
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Humans
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Jurkat Cells
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Lymphocyte Activation / drug effects*
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Receptors, Antigen, T-Cell / agonists
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Receptors, Antigen, T-Cell / drug effects*
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Receptors, Antigen, T-Cell / metabolism*
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
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Tetradecanoylphorbol Acetate / pharmacology
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src-Family Kinases / physiology
Substances
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CD3 Complex
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Receptors, Antigen, T-Cell
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Protein-Tyrosine Kinases
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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src-Family Kinases
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Protein Kinase C
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Tetradecanoylphorbol Acetate