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)bet a locus is tightly regulated. Here, we describe a system in which TCR beta allelic exclusion is overcome as a result of V(D)J recombination in periphe ral CD4(+) T cells. In TCR beta chain transgenic mice, tolerogen-mediated c hronic peripheral selection against cells expressing the transgene leads to surface expression of endogenous TCR beta chains. Peripheral CD4(+) T cell s reexpress the recombination activating genes, RAG1 and RAG2, and contain signal end intermediates indicative of ongoing V(D)J recombination. The res cue from deletion of mature T cells expressing newly generated TCR beta cha ins suggests that receptor revision plays a role in the maintenance of peri pheral T cell tolerance.