Superantigen-induced TCR alpha locus secondary rearrangement: role in tolerance induction |
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Authors: | Huang Ching-Yu Golub Rachel Wu Gillian E Kanagawa Osami |
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Institution: | Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. |
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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. |
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