Abstract
Small changes in the peptide-major histocompatibility complex (MHC) molecule ligands recognized by antigen-specific T cell receptors (TCRs) can convert fully activating complexes into partially activating or even inhibitory ones. This study examined early TCR-dependent signals induced by such partial agonists or antagonists. In contrast to typical agonist ligands, both an antagonist and several partial agonists stimulated a distinct pattern of zeta chain phosphorylation and failed to activate associated ZAP-70 kinase. These results identify a specific step in the early tyrosine phosphorylation cascade that is altered after TCR engagement with modified peptide-MHC molecule complexes. This finding may explain the different biological responses to TCR occupancy by these variant ligands.
MeSH terms
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Amino Acid Sequence
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Animals
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Clone Cells
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Cytochrome c Group / pharmacology
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Enzyme Activation
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / pharmacology*
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Interleukin-2 / biosynthesis
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L Cells
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Ligands
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Lymphocyte Activation
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Membrane Proteins / metabolism*
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Mice
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Molecular Sequence Data
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Mutation
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Peptide Fragments / pharmacology
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Phosphorylation
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Antigen, T-Cell / agonists
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Receptors, Antigen, T-Cell / antagonists & inhibitors
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction
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T-Lymphocytes, Helper-Inducer / immunology*
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Tyrosine / metabolism
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ZAP-70 Protein-Tyrosine Kinase
Substances
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Cytochrome c Group
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Histocompatibility Antigens Class II
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Interleukin-2
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Ligands
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Membrane Proteins
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Peptide Fragments
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Receptors, Antigen, T-Cell
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antigen T cell receptor, zeta chain
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Tyrosine
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Protein-Tyrosine Kinases
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ZAP-70 Protein-Tyrosine Kinase
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Zap70 protein, mouse