Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+) thymocytes.

Published

Journal Article

T cell receptor (TCR) alpha alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCRalpha rearrangement in orphan nuclear receptor RORgamma-deficient mice, in which the DP lifespan is shorter, and in Bcl-x(L)-transgenic mice, in which the DP lifespan is extended, we show that the progression of secondary V(alpha) to J(alpha) rearrangements is controlled by DP thymocyte survival. In addition, because Bcl-x(L) induces a bias towards 3' J(alpha) usage in peripheral T cells, we conclude that the programmed cell death of DP thymocytes is not simply a consequence of failed positive selection. Rather, it limits the progression of rearrangement along the J(alpha) locus and the opportunities for positive selection, thereby regulating the TCRalpha repertoire.

Full Text

Duke Authors

Cited Authors

  • Guo, J; Hawwari, A; Li, H; Sun, Z; Mahanta, SK; Littman, DR; Krangel, MS; He, Y-W

Published Date

  • May 2002

Published In

Volume / Issue

  • 3 / 5

Start / End Page

  • 469 - 476

PubMed ID

  • 11967541

Pubmed Central ID

  • 11967541

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni791

Language

  • eng