Fig. 5.

Proposed mechanism by which IL-15 mediates antigen-independent avidity maturation of CD8⁺ T cells by both instruction at the individual cell level and selection at the population level. High-avidity CTLs are induced to express high levels of IL-15Rα, either by a strong signal through the TCR and costimulatory receptors (signals 1 and 2, respectively) or by selection or induction by IL-15 during priming (IL-15 in a vaccine or produced by dendritic cells). These high-avidity CTLs are thus more sensitive to low endogenous levels of IL-15, which then promotes preferential survival and homeostatic proliferation of the high-avidity CTLs, resulting in selection of a higher average avidity at the population level, or induces up-regulation of CD8αβ coreceptor, resulting in increased functional avidity at the individual cell level.