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

Nat Immunol. 2002 May;3(5):469-76. doi: 10.1038/ni791. Epub 2002 Apr 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cell Survival / immunology
  • Chromatin / immunology
  • DNA / chemistry
  • DNA / genetics
  • DNA / isolation & purification
  • Flow Cytometry
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / immunology*
  • Receptors, Retinoic Acid*
  • Receptors, Thyroid Hormone*
  • Specific Pathogen-Free Organisms
  • bcl-X Protein


  • Bcl2l1 protein, mouse
  • Chromatin
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • bcl-X Protein
  • DNA