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Superantigen-Induced TCR Locus Secondary Rearrangement: Role in Tolerance Induction¹

Ching-Yu Huang^*, Rachel Golub^,, Gillian E. Wu and Osami Kanagawa^2,*

^* Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; Laboratoire d’Immunobiologie, Université Denis Diderot, Paris, France; and Departments of Immunology and Medial Biophysics and Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada

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 knock-in mouse in which the knock-in -chain can be replaced with endogenous -chain through secondary rearrangement, we show that immunization of superantigen changes the TCR -chain expression on peripheral superantigen-specific T cells, induces expression of recombination-activating genes, and generates DNA double-strand breaks at the TCR -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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