Adaptive immunity after cell death

•The immunogenicity of dead cells depends on the exposure or release of damage-associated molecular patterns (DAMPs).•DAMPs are detected by receptors that are thought to signal to activate dendritic cells.•Some DAMP receptors selectively regulate antigen processing and presentation.•DAMP receptors are nonredundant players in immunity to injury or infection.

We understand much about the agents, receptors, and signalling pathways that lead to immunity to pathogens. Less is known about how the process is initiated in apparently sterile conditions such as spontaneous immunity to certain tumours, tissue grafts, or autoimmune disorders. Proinflammatory molecules released by dying cells, termed damage-associated molecular patterns (DAMPs), have been proposed to activate dendritic cells (DCs) to promote T cell responses to antigens present in cell corpses. Surprisingly, rather than affecting activation, some recently identified DAMP receptors control specialised DC functions such as antigen acquisition and presentation. This selectivity reveals a new point of control in the regulation of adaptive immunity and, potentially, tolerance that renders DAMPs nonredundant players in responses to both sterile and nonsterile insults.