Regulation of T cell receptor beta allelic exclusion at a level beyond accessibility.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Jackson, A; Kondilis, HD; Khor, B; Sleckman, BP; Krangel, MS

Published Date

  • February 2005

Published In

Volume / Issue

  • 6 / 2

Start / End Page

  • 189 - 197

PubMed ID

  • 15640803

Pubmed Central ID

  • 15640803

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni1157

Language

  • eng

Conference Location

  • United States