FIGURE 9.

Trans-presented IL-15 improves the sensitivity and magnitude of the antigen-specific CD8⁺ response and synergizes with additional cytokine signals. a, a nanoparticle-based artificial APC was used to investigate the effect of surface-retained IL-15:IL-15Rα on antigen presentation. b, aAPCs were compared with DCs loaded with antigen-encapsulating NPs for their ability to stimulate CD8⁺ T cells. c, T cell stimulation was assessed by cell proliferation (left panel) and IFN-γ secretion (right panel). Next we assessed the effect of IL-15 trans-presentation on aAPCs. Biotinylated, SIINFEKL-loaded H2-Kb MHC I dimers were titrated on all nanoparticle groups along with equimolar concentrations of anti-CD28. This was done in the presence or absence of surface-bound IL-15:IL-15Rα. The resulting constructs were co-incubated with OT-I CD8⁺ T cells, and T cell proliferation was assessed. d—f, data for cell proliferation (left panels) and IFN-γ secretion (right panels) are shown for three different experiments: blank nanoparticles (d), blank nanoparticles with 5 ng/ml of exogenous IL-2 (e), and nanoparticles encapsulating 0.5 ng/mg of encapsulated IL-2 (f).