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

Christopher Howe, Malgorzata Garstka, Mohammed Al-Balushi, Esther Ghanem, Antony N. Antoniou, Susanne Fritzsche, Gytis Jankevicius, Nasia Kontouli, Clemens Schneeweiss, Anthony Williams, Tim Elliott*, Sebastian Springer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3730-3744
Number of pages15
JournalEMBO Journal
Issue number23
Publication statusPublished - Dec 2009


  • Calreticulin
  • Endoplasmic reticulum
  • Major histocompatibility complex (MHC) class I molecules
  • Peptides
  • Quality control

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology


Dive into the research topics of 'Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class i molecules'. Together they form a unique fingerprint.

Cite this