Clonal Deletion Prunes but Does Not Eliminate Self-Specific [alpha][beta] CD8+ T Lymphocytes.
Yu, Wong 1,2; Jiang, Ning 3,8; Ebert, Peter J.R. 1; Kidd, Brian A. 1,9; Muller, Sabina 4; Lund, Peder J. 1; Juang, Jeremy 1; Adachi, Keishi 1,10; Tse, Tiffany 1; Birnbaum, Michael E. 1; Newell, Evan W. 1,11; Wilson, Darrell M. 5; Grotenbreg, Gijsbert M. 6,12; Valitutti, Salvatore 4; Quake, Stephen R. 3,7; Davis, Mark M. 1,7,*
[Article]
Immunity.
42(5):929-941, May 19, 2015.
(Format: HTML, PDF)
SUMMARY: 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.
Highlights:
* 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.
(C) 2015Elsevier, Inc.