Reconstitution of glycan-driven MHC-I recycling reveals calreticulin as mediator between TAPBPR and tapasin.

Calreticulin mediates glycan-dependent transfer of MHC-I from TAPBPR to tapasin, revealing a glycan-surveillance mechanism in ER quality control.

• Why it matters: Understanding how glycan-dependent processes coordinate MHC-I maturation is crucial for insights into immune function and protein quality control in the ER, addressing a key gap in the field.
• What they did: Using a fully reconstituted system, the study demonstrates that calreticulin recognizes monoglucosylated MHC-I glycans to facilitate retrograde transfer from TAPBPR to tapasin, with the C-terminal acidic helix being essential for docking but not release.
• The result: These findings define a glycan-dependent chaperone network that ensures efficient MHC-I maturation, highlighting fundamental principles of ER protein quality control and immune presentation.