Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class I molecules.
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.
Cancer Sciences Division, University of Southampton School of Medicine, Southampton, UK.
Christopher
C
Howe
Malgorzata
M
Garstka
Mohammed
M
Al-Balushi
Esther
E
Ghanem
Antony N
AN
Antoniou
Susanne
S
Fritzsche
Gytis
G
Jankevicius
Nasia
N
Kontouli
Clemens
C
Schneeweiss
Anthony
A
Williams
Tim
T
Elliott
Sebastian
S
Springer
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D037282:Calreticulin / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006183:H-2 Antigens / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
D037282:Calreticulin; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D010455:Peptides