Clonal Deletion Prunes but Does Not Eliminate Self-Specific αβ 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 J.R., Kidd, Brian A., Müller, 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: 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
• ISSN: 1074-7613; 1097-4180
• 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. •Similar numbers of human blood CD8+ T cells recognize self versus novel foreign antigens•H-Y T cells in men are 1/3 as frequent as in women but have similar functional avidity•Self-specific CD8+ T cells are resistant to activation and/or expansion•Inefficient self-specific T cell deletion might allow better protection from infection Clonal deletion is thought to efficiently remove almost all self-specific T cells. Davis and colleagues find instead that many human CD8+ T cells specific for endogenous peptides escape deletion and are anergic. They propose that the inefficient deletion of self-specific T cells might allow for better protection against infection.