Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class I molecules

EMBO J. 2009 Dec 2;28(23):3730-44. doi: 10.1038/emboj.2009.296. Epub 2009 Oct 22.


Calreticulin is a lectin chaperone of the endoplasmic reticulum (ER). In calreticulin-deficient cells, major histocompatibility complex (MHC) class I molecules travel to the cell surface in association with a sub-optimal peptide load. Here, we show that calreticulin exits the ER to accumulate in the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi, together with sub-optimally loaded class I molecules. Calreticulin that lacks its C-terminal KDEL retrieval sequence assembles with the peptide-loading complex but neither retrieves sub-optimally loaded class I molecules from the cis-Golgi to the ER, nor supports optimal peptide loading. Our study, to the best of our knowledge, demonstrates for the first time a functional role of intracellular transport in the optimal loading of MHC class I molecules with antigenic peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Calreticulin / metabolism
  • Calreticulin / physiology*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cricetinae
  • Endoplasmic Reticulum / metabolism
  • Golgi Apparatus / metabolism
  • H-2 Antigens / metabolism*
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / metabolism*
  • Protein Binding / physiology
  • Protein Transport / physiology
  • Rats
  • Signal Transduction / physiology*


  • Calreticulin
  • H-2 Antigens
  • H-2Kb protein, mouse
  • Peptides