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

Academic Article

Abstract

  • Allelic exclusion of Vβ-to-DJβ recombination depends on asynchronous rearrangement of alleles of the gene encoding T cell receptor β in double-negative thymocytes and feedback inhibition that is maintained in double-positive thymocytes. Feedback is thought to be enforced through downregulation of Vβ accessibility. In an attempt to override this negative regulation, we introduced the enhancer of the gene encoding T cell receptor α into the Vβ gene cluster downstream of Vβ12. In double-negative thymocytes, the introduced enhancer had no measurable effect on accessibility, but Vβ12 rearrangement was stimulated and Vβ12 allelic exclusion was partially subverted. In contrast, double-positive thymocytes showed increased Vβ transcription and accessibility, but feedback inhibition of Vβ-to-DJβ recombination remained intact. Our results indicate additional regulatory constraints on Vβ-to-DJβ recombination that operate beyond the accessibility barrier.
  • Authors

    Published In

  • Nature Immunology  Journal
  • Digital Object Identifier (doi)

    Author List

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

  • 189
  • End Page

  • 197
  • Volume

  • 6
  • Issue

  • 2