Cutting Edge: Rag Deletion in Peripheral T Cells Blocks TCR Revision

Mature CD4(+)V beta 5(+) T cells that recognize a peripherally expressed endogenous superantigen are tolerized either by deletion or TCR revision. In V beta 5 transgenic mice, this latter tolerance pathway results in the appearance of CD4(+)V beta 5(-)TCR beta(+) T cells, coinciding with Rag1, Rag2, and TdT expression and the accumulation of V-beta-DJ(beta) recombination intermediates in peripheral CD4(+) T cells. Because postthymic RAG-dependent TCR rearrangement has remained controversial, we sought to definitively determine whether TCR revision is an extrathymic process that occurs in mature peripheral T cells. We show in this study that Rag deletion in postpositive selection T cells in V beta 5 transgenic mice blocks TCR revision in vivo and that mature peripheral T cells sorted to remove cells bearing endogenous TCR beta-chains can express newly generated TCR beta molecules in adoptive hosts. These findings unambiguously demonstrate postthymic, RAG-dependent TCR rearrangement and define TCR revision as a tolerance pathway that targets mature peripheral CD4(+) T cells. The Journal of Immunology, 2010, 184: 5964-5968.