Figure 1. Activation of the T-cell receptor (TCR) by contact with the target cell results in Ca²⁺ signals in the CTL: (1) the second messenger, NAADP, is synthesized; (2) NAADP activates target TPCs (two-pore channels) on the acidic cytolytic granules themselves; (3) TPCs generate local Ca²⁺ domains around the granules that act in concert with the ER/Ca²⁺ influx pathway to evoke exocytosis (4).