Abstract
Binding of peptide/MHC (pMHC) complexes by TCR initiates T cell activation. Despite long interest, the exact relationship between the biochemistry of TCR/pMHC interaction (particularly TCR affinity or ligand off-rate) and T cell responses remains unresolved, because the number of complexes examined in each independent system has been too small to draw a definitive conclusion. To test the current models of T cell activation, we have analyzed the interactions between the mouse P14 TCR and a set of altered peptides based on the lymphocytic choriomeningitis virus epitope gp33-41 sequence bound to mouse class I MHC D(b). pMHC binding, TCR-binding characteristics, CD8+ T cell cytotoxicity, and IFN-gamma production were measured for the peptides. We found affinity correlated well with both cytotoxicity and IFN-gamma production. In contrast, no correlation was observed between any kinetic parameter of TCR-pMHC interaction and cytotoxicity or IFN-gamma production. This study strongly argues for an affinity threshold model of T cell activation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, Viral / genetics
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Antigens, Viral / immunology*
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Antigens, Viral / pharmacology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology*
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Cytotoxicity, Immunologic
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Glycoproteins / genetics
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Glycoproteins / immunology*
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Glycoproteins / pharmacology
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / metabolism*
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Interferon-gamma / metabolism
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Kinetics
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Lymphocyte Activation*
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Mutation
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Peptide Fragments / genetics
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Peptide Fragments / immunology*
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Peptide Fragments / pharmacology
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Receptors, Antigen, T-Cell / immunology*
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T-Lymphocytes, Cytotoxic / immunology
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Viral Proteins / genetics
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Viral Proteins / immunology*
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Viral Proteins / pharmacology
Substances
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Antigens, Viral
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Glycoproteins
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Histocompatibility Antigens Class I
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Viral Proteins
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glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
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Interferon-gamma