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

Membrane-anchored perforin-2 is essential for antigen escape into the cytosol, with full-length protein mediating endocytic escape in immune cells.

• Why it matters: Understanding how perforin-2 controls pore formation without compromising endocytic compartment integrity is crucial for insights into immune defense and antigen presentation mechanisms.
• What they did: The study used proteolytic analysis and functional assays to show that full-length, membrane-anchored perforin-2, not its cleaved ectodomain, facilitates antigen escape, independent of pH changes.
• The result: Findings highlight the importance of the transmembrane domain in perforin-2 function, enabling distinct mechanisms for bacterial defense and antigen cross-presentation, which could inform immune response modulation.