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 journalArticlepeer-review

62 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)3730-44
Number of pages15
JournalEMBO Journal
Volume28
Issue number23
DOIs
Publication statusPublished - 2 Dec 2009

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