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

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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
Volume28
Issue number23
DOIs
Publication statusPublished - Dec 2009

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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  • Cite this

    Howe, C., Garstka, M., Al-Balushi, M., Ghanem, E., Antoniou, A. N., Fritzsche, S., Jankevicius, G., Kontouli, N., Schneeweiss, C., Williams, A., Elliott, T., & Springer, S. (2009). Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class i molecules. EMBO Journal, 28(23), 3730-3744. https://doi.org/10.1038/emboj.2009.296