Regulation of TCRβ allelic exclusion by gene segment proximity and accessibility.

Published

Journal Article

Ag receptor loci are regulated to promote allelic exclusion, but the mechanisms are not well understood. Assembly of a functional TCR β-chain gene triggers feedback inhibition of V(β)-to-DJ(β) recombination in double-positive (DP) thymocytes, which correlates with reduced V(β) chromatin accessibility and a locus conformational change that separates V(β) from DJ(β) gene segments. We previously generated a Tcrb allele that maintained V(β) accessibility but was still subject to feedback inhibition in DP thymocytes. We have now further analyzed the contributions of chromatin accessibility and locus conformation to feedback inhibition using two novel TCR alleles. We show that reduced V(β) accessibility and increased distance between V(β) and DJ(β) gene segments both enforce feedback inhibition in DP thymocytes.

Full Text

Duke Authors

Cited Authors

  • Kondilis-Mangum, HD; Shih, H-Y; Mahowald, G; Sleckman, BP; Krangel, MS

Published Date

  • December 15, 2011

Published In

Volume / Issue

  • 187 / 12

Start / End Page

  • 6374 - 6381

PubMed ID

  • 22079986

Pubmed Central ID

  • 22079986

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1102611

Language

  • eng

Conference Location

  • United States