First Author | Jackson A | Year | 2005 |
Journal | Nat Immunol | Volume | 6 |
Issue | 2 | Pages | 189-97 |
PubMed ID | 15640803 | Mgi Jnum | J:95669 |
Mgi Id | MGI:3526765 | Doi | 10.1038/ni1157 |
Citation | Jackson A, et al. (2005) Regulation of T cell receptor beta allelic exclusion at a level beyond accessibility. Nat Immunol 6(2):189-97 |
abstractText | 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. |