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)beta locus is tightly regulated. Here, we describe a system in which TCRbeta allelic exclusion is overcome as a result of V(D)J recombination in peripheral CD4+ T cells. In TCRbeta chain transgenic mice, tolerogen-mediated chronic peripheral selection against cells expressing the transgene leads to surface expression of endogenous TCRbeta 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 TCRbeta chains suggests that receptor revision plays a role in the maintenance of peripheral T cell tolerance.
McMahan
C J
CJ
Department of Immunology, University of Washington School of Medicine, Seattle 98195, USA.
Fink
P J
PJ
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D004274:DNA, Recombinant / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D019674:Genes, T-Cell Receptor beta; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011995:Recombination, Genetic; D019076:Transgenes
D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein