Anchoring of perforin-2 via the transmembrane domain is required for antigen escape into the cytosol.

Full-length, membrane-anchored perforin-2 is required for antigen escape into the cytosol in dendritic cells, not the proteolytically released ectodomain.

• Why it matters: Understanding how perforin-2 controls pore formation while preserving endocytic compartment integrity is crucial for insights into immune responses and antigen presentation mechanisms.
• What they did: The study examined perforin-2 in dendritic cells, showing that it undergoes proteolytic processing but that antigen escape depends on full-length, membrane-anchored perforin-2 rather than its cleaved ectodomain, and that pore formation does not require low pH.
• The result: These findings highlight the essential role of the transmembrane anchor in perforin-2 function and suggest distinct mechanisms for pore formation during bacterial defense and cross-presentation.