T-cell-specific deletion of T-cell receptor transgenes allows functional rearrangement of endogenous alpha- and beta-genes

Nature. 1988 Jul 14;334(6178):156-9. doi: 10.1038/334156a0.


In B cells the loci encoding immunoglobulin chains usually show allelic exclusion; a given B cell transcribes and translates only one productively rearranged allele of the heavy and light chain loci. This ensures that each B cell expresses only one antigen receptor. The loci encoding T-cell receptor (TCR) alpha- and beta-genes may behave similarly. We have previously reported that the expression of a transgenic TCR beta-chain prevents functional and nonfunctional V beta rearrangements in the endogenous beta-chain loci but not D beta J beta rearrangements. We have also been unable to detect the expression of the TCR gamma-chain locus in thymocytes of these mice (unpublished observations). To study the mechanisms involved in forming a mature T-cell repertoire further, we have constructed mice expressing alpha- and beta-TCR transgenes derived from a cytotoxic T-cell clone that is specific for the male antigen H-Y in the context of H-2Db MHC molecules. Here we show that in these mice rearrangement of endogenous alpha-chain loci is also suppressed, although to a lesser extent than rearrangement of beta-chain loci. In addition, in male alpha beta TCR transgenic mice we observed T-cell clones which had deleted both transgenic alpha- and beta-chain genes and expressed endogenous alpha- and beta-chain TCR genes. These cells are presumably derived from rare thymocytes that leave the male thymus because their TCR no longer recognizes self antigen. The vast majority of CD4+8+ nonmature thymocytes expressing alpha- and beta-transgenes are deleted in the male thymus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Deletion
  • Cytotoxicity, Immunologic
  • Female
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Transgenic / physiology*
  • Receptors, Antigen, T-Cell / genetics*
  • Recombination, Genetic
  • T-Lymphocytes / classification
  • T-Lymphocytes / physiology*
  • Tissue Distribution
  • Transcription, Genetic


  • Receptors, Antigen, T-Cell