Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells

Supramolecular attack particles Cytotoxic T cells (CTLs) are at the front lines against cancer and chronic infection. T cells kill by secreting caspase-activating granzymes and the pore-forming protein perforin from dense core granules. However, the structural basis of lethal hit delivery has remained unknown. Balint et al. enriched the synaptic output of CTLs to investigate the released form of perforin and granzyme B. They found that CTLs released perforin and granzymes in stable particles called supramolecular attack complexes or SMAPs. The SMAPs were composed of a core shell structure and were assembled in the CTL dense secretory granules before release. The released SMAPs showed an innate ability to kill target cells. Science , this issue p. 897