RAG Reexpression and DNA Recombination at T Cell Receptor Loci in Peripheral CD4 + T Cells

Under most circumstances, allelic exclusion at the T cell receptor (TCR)β locus is tightly regulated. Here, we describe a system in which TCRβ allelic exclusion is overcome as a result of V(D)J recombination in peripheral CD4 + T cells. In TCR β chain transgenic mice, tolerogen-mediated chronic peripheral selection against cells expressing the transgene leads to surface expression of endogenous TCR β chains. Peripheral CD4 + T cells reexpress the recombination activating genes, RAG1 and RAG2, and contain signal end intermediates indicative of ongoing V(D)J recombination. The rescue from deletion of mature T cells expressing newly generated TCR β chains suggests that receptor revision plays a role in the maintenance of peripheral T cell tolerance.