Clonal Deletion Prunes but Does Not Eliminate Self-Specific alpha beta CD8+ T Lymphocytes

• Published in: Immunity (Cambridge, Mass.) Mass.), 2015-05, Vol.42 (5), p.929-941
• Main Authors: Yu, Wong, Jiang, Ning, Ebert, Peter JR, Kidd, Brian A, Mueller, Sabina, Lund, Peder J, Juang, Jeremy, Adachi, Keishi, Tse, Tiffany, Birnbaum, Michael E, Newell, Evan W, Wilson, Darrell M, Grotenbreg, Gijsbert M, Valitutti, Salvatore, Quake, Stephen R, Davis, Mark M
• Format: Article
• Language: English
• Subjects: Hepatitis C virus
• ISSN: 1074-7613
• 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.