Essential role of the pre-T cell receptor in allelic exclusion of the T cell receptor beta locus

Immunity. 1997 Nov;7(5):601-7. doi: 10.1016/s1074-7613(00)80381-7.

Abstract

Following the recent realization that TCR beta transgenes can severely inhibit the rearrangement of endogenous Vbeta gene segments in the absence of pre-TCR alpha (pT alpha) chains, we tested whether the pre-TCR has an essential role in TCR beta allelic exclusion under more physiological conditions by analyzing TCR rearrangement in immature thymocytes by single-cell PCR. Our results in pT alpha+ mice are consistent with an ordered model of TCR beta rearrangement beginning on one allele and continuing on the other only when the first attempt is unsuccessful. By contrast, a higher proportion of thymocytes from pT alpha-/- mice exhibited two productive TCR beta alleles. Thus, the pre-TCR-independent suppression of rearrangement by TCR beta transgenes represents a transgene artifact, whereas under physiological conditions the pre-TCR is essential for allelic exclusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Cell Differentiation
  • Gene Expression Regulation, Developmental
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor*
  • Genes, T-Cell Receptor alpha*
  • Genes, T-Cell Receptor beta*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Polymerase Chain Reaction / methods
  • Protein Processing, Post-Translational
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / physiology*
  • T-Lymphocytes / cytology*
  • Thymus Gland / cytology*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta