Superantigen-induced TCR alpha locus secondary rearrangement: role in tolerance induction

J Immunol. 2002 Apr 1;168(7):3259-65. doi: 10.4049/jimmunol.168.7.3259.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens / pharmacology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Columbidae
  • Cytochrome c Group / immunology
  • Cytochrome c Group / pharmacology
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / immunology*
  • Genes, T-Cell Receptor alpha / immunology*
  • Immune Tolerance / genetics*
  • Immunization
  • Injections, Intravenous
  • Lymphocyte Activation / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta / antagonists & inhibitors
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Spleen / cytology
  • Spleen / immunology
  • Superantigens / administration & dosage
  • Superantigens / immunology*
  • Superantigens / pharmacology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • Antigens
  • Cytochrome c Group
  • Receptors, Antigen, T-Cell, alpha-beta
  • Superantigens