Clonal Deletion Prunes but Does Not Eliminate Self-Specific αβ CD8(+) T Lymphocytes

Immunity. 2015 May 19;42(5):929-41. doi: 10.1016/j.immuni.2015.05.001.


It has long been thought that clonal deletion efficiently removes almost all self-specific T cells from the peripheral repertoire. We found that self-peptide MHC-specific CD8(+) T cells in the blood of healthy humans were present in frequencies similar to those specific for non-self antigens. For the Y chromosome-encoded SMCY antigen, self-specific T cells exhibited only a 3-fold lower average frequency in males versus females and were anergic with respect to peptide activation, although this inhibition could be overcome by a stronger stimulus. We conclude that clonal deletion prunes but does not eliminate self-specific T cells and suggest that to do so would create holes in the repertoire that pathogens could readily exploit. In support of this hypothesis, we detected T cells specific for all 20 amino acid variants at the p5 position of a hepatitis C virus epitope in a random group of blood donors.

Publication types

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

MeSH terms

  • Animals
  • Antigenic Variation
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Clonal Deletion*
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Mice
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Self Tolerance / immunology


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