Superantigen-induced TCR alpha locus secondary rearrangement: role in tolerance induction.
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.
Huang
Ching-Yu
CY
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Golub
Rachel
R
Wu
Gillian E
GE
Kanagawa
Osami
O
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology / Q000494:pharmacology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000276:immunology*; D019673:Genes, T-Cell Receptor alpha / Q000276:immunology*; D007108:Immune Tolerance / Q000235:genetics*; D007114:Immunization; D007275:Injections, Intravenous; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D000941:Antigens; D003574:Cytochrome c Group; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens