Abstract
Immunization with superantigen in vivo induces transient activation of superantigen-specific T cells, followed by a superantigen-nonresponsive state. In this study, using a TCR alpha knock-in mouse in which the knock-in alpha-chain can be replaced with endogenous alpha-chain through secondary rearrangement, we show that immunization of superantigen changes the TCR alpha-chain expression on peripheral superantigen-specific T cells, induces expression of recombination-activating genes, and generates DNA double-strand breaks at the TCR alpha-chain locus. These results suggest that viral superantigens are capable of inducing peripheral TCR revision. Our findings thus provide a new perspective on pathogen-immune system interaction.
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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Animals
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Antigens / pharmacology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Columbidae
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Cytochrome c Group / immunology
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Cytochrome c Group / pharmacology
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Down-Regulation / genetics
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Down-Regulation / immunology
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Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / immunology*
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Genes, T-Cell Receptor alpha / immunology*
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Immune Tolerance / genetics*
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Immunization
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Injections, Intravenous
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Lymphocyte Activation / genetics*
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Knockout
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Mice, Transgenic
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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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Spleen / cytology
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Spleen / immunology
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Superantigens / administration & dosage
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Superantigens / immunology*
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Superantigens / pharmacology
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
Substances
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Antigens
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Cytochrome c Group
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Receptors, Antigen, T-Cell, alpha-beta
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Superantigens