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Keywords:

  • Thymocyte development;
  • Gene rearrangement;
  • Gene regulation;
  • TCR;
  • Repertoire development

Abstract

CD4CD8 thymocytes expressing a transgenic T cell receptor (TCR) α  chain have decreased capacity to give rise to CD4+CD8+ thymocytes when compared with wild-type thymocytes. This inefficient CD4CD8 to CD4+CD8+ maturation is mediated by the transgenic TCR α  chain pairing with endogenous TCR β  chain but not with endogenous TCR γ  chain. Comparison between TCR α  chain-transgenic mice with or without a functional pre-TCR α  (pTα ) chain reveals that the formation of transgenic α /endogenous β  TCR on CD4CD8 thymocytes inhibits the formation of pre-TCR, but at the same time mediates CD4CD8 to CD4+CD8+ maturation in the absence of pre-TCR, albeit inefficiently. These results indicate that α β  TCR and pre-TCR provide different signals for thymocyte development. They also suggest that the precise regulation of the sequential rearrangements of TCR β  and α  loci and the cellular expansion induced by the pre-TCR may both be evolved to ensure the efficient generation of mature α β  T cells.