The first step in an adaptive immune response (one tailored to individual pathogens) is maturation of dendritic cells (DCs). These cells live in peripheral tissues and, when microbial products bind to their Toll-like receptors (TLRs), they mature into antigen-presenting cells. These then migrate to lymph nodes, where they stimulate naive T cells. An increase in intracellular Ca²⁺ is also involved in DC maturation, but what drives Ca²⁺ release? On p. 2232, Susan Treves and co-authors provide the first evidence that the type 1 ryanodine receptor (RyR1), an intracellular Ca²⁺ channel found mainly in skeletal muscle, is involved in DC maturation. They show that treatment of immature DCs with the RyR1 agonist caffeine increases intracellular Ca²⁺ levels and that concomitant treatment of these cells with caffeine and suboptimal amounts of TLR ligands leads to DC maturation and stimulation of T-cell functions. The authors propose, therefore, that DC maturation involves cooperation between RyR1-mediated and TLR-mediated signalling, particularly when the levels of TLR ligands are suboptimal.