Regulation of T cell receptor beta allelic exclusion at a level beyond accessibility.
Allelic exclusion of V(beta)-to-DJ(beta) recombination depends on asynchronous rearrangement of alleles of the gene encoding T cell receptor beta in double-negative thymocytes and feedback inhibition that is maintained in double-positive thymocytes. Feedback is thought to be enforced through downregulation of V(beta) accessibility. In an attempt to override this negative regulation, we introduced the enhancer of the gene encoding T cell receptor alpha into the V(beta) gene cluster downstream of V(beta)12. In double-negative thymocytes, the introduced enhancer had no measurable effect on accessibility, but V(beta)12 rearrangement was stimulated and V(beta)12 allelic exclusion was partially subverted. In contrast, double-positive thymocytes showed increased V(beta) transcription and accessibility, but feedback inhibition of V(beta)-to-DJ(beta) recombination remained intact. Our results indicate additional regulatory constraints on V(beta)-to-DJ(beta) recombination that operate beyond the accessibility barrier.
Jackson
Annette
A
The Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Kondilis
Hrisavgi D
HD
Khor
Bernard
B
Sleckman
Barry P
BP
Krangel
Michael S
MS
D000483:Alleles; D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014158:Transcription, Genetic / Q000235:genetics
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D016693:Receptors, Antigen, T-Cell, alpha-beta