TCR alpha-chain repertoire in pTalpha-deficient mice is diverse and developmentally regulated: implications for pre-TCR functions and TCRA gene rearrangement

J Immunol. 1999 Dec 1;163(11):6053-9.

Abstract

Pre-TCR expression on developing thymocytes allows cells with productive TCRB gene rearrangements to further differentiate. In wild-type mice, most TCRA gene rearrangements are initiated after pre-TCR expression. However, in pTalpha-deficient mice, a substantial number of alphabeta+ thymocytes are still produced, in part because early TCR alpha-chain expression can rescue immature thymocytes from cell death. In this study, the nature of these TCR alpha-chains, produced and expressed in the absence of pre-TCR expression, have been analyzed. We show, by FACS analysis and sequencing of rearranged transcripts, that the TCRA repertoire is diverse in pTalpha-/- mice and that the developmental regulation of AJ segment use is maintained, yet slightly delayed around birth when compared with wild-type mice. We also found that T cell differentiation is more affected by pTalpha inactivation during late gestation than later in life. These data suggest that the pre-TCR is not functionally required for the initiation and regulation of TCRA gene rearrangement and that fetal thymocytes are more dependent than adult cells on pTalpha-derived signals for their differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cloning, Molecular
  • Flow Cytometry
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor*
  • Genes, T-Cell Receptor alpha*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Mutant Strains
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, alpha-beta / deficiency*
  • Sequence Analysis, DNA
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology
  • Thymus Gland / cytology
  • Thymus Gland / embryology
  • Thymus Gland / growth & development*

Substances

  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • pre-T cell receptor alpha