A Role for TCR Affinity in Regulating Naive T Cell Homeostasis

Abstract Homeostatic signals that control the overall size and composition of the naive T cell pool have recently been identified to arise from contact with self-MHC/peptide ligands and a cytokine, IL-7. IL-7 presumably serves as a survival factor to keep a finite number of naive cells alive by preventing the onset of apoptosis, but how TCR signaling from contact with self-MHC/peptide ligands regulates homeostasis is unknown. To address this issue, murine polyclonal and TCR-transgenic CD8+ cells expressing TCR with different affinities for self-MHC/peptide ligands, as depicted by the CD5 expression level, were analyzed for their ability to respond to and compete for homeostatic factors under normal and lymphopenic conditions. The results suggest that the strength of the TCR affinity determines the relative “fitness” of naive T cells to compete for factors that support cell survival and homeostatic proliferation.