Abstract
Some ligand-receptor systems have a receptor reserve where a maximal response can be achieved by occupation of a fraction of available receptors. An implication of a receptor reserve is the expansion of the number of ligands for response. To determine whether T cells follow receptor reserve, we have characterized the effect of reducing TCR levels on CD4 T cell responses elicited by altered peptide ligands that vary in potency. Agonist peptide is unaffected by a 90% reduction in TCR level while proliferation to weak agonists is significantly inhibited when TCR expression is reduced by 40%. Thymocyte-negative selection similarly demonstrates a differential requirement of TCR for response to agonist, weak agonist, and partial agonist. Therefore, our data demonstrate receptor reserve as a novel principle of T cell activation in which excess TCRs expand the antigenic repertoire to include less potent ligands.
Publication types
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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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Amino Acid Sequence
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Animals
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Antibodies, Blocking / pharmacology
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Antigens, CD / biosynthesis
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Antigens, Differentiation, T-Lymphocyte / biosynthesis
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism*
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Cytochrome c Group / immunology
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Cytochrome c Group / pharmacology
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Dose-Response Relationship, Immunologic
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Down-Regulation / genetics
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Down-Regulation / immunology
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Growth Inhibitors / antagonists & inhibitors
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Growth Inhibitors / biosynthesis
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Growth Inhibitors / genetics
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Growth Inhibitors / immunology
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Immunoglobulin Fab Fragments / pharmacology
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Lectins, C-Type
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Ligands
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Lymphocyte Activation* / genetics
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Mice
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Mice, Inbred A
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Mice, Inbred C57BL
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Mice, Transgenic
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Molecular Sequence Data
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Moths / enzymology
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Receptors, Antigen, T-Cell, alpha-beta / antagonists & inhibitors
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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T-Lymphocyte Subsets / cytology
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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 / immunology
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Up-Regulation / immunology
Substances
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Antibodies, Blocking
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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Cytochrome c Group
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Growth Inhibitors
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Immunoglobulin Fab Fragments
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Lectins, C-Type
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Ligands
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Receptors, Antigen, T-Cell, alpha-beta