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

Calreticulin mediates glycan-dependent MHC-I recycling, enabling efficient immune molecule maturation with a critical role in TAPBPR-tapasin transfer.

• Why it matters: Understanding how glycan-dependent mechanisms coordinate MHC-I transfer is vital for insights into immune system function and ER quality control, addressing a key gap in cellular immunology.
• 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 helix being essential for docking.
• The result: This reveals a glycan-surveillance pathway that retrieves suboptimally loaded MHC-I molecules, highlighting a finely tuned chaperone network crucial for proper immune molecule maturation and ER quality control.