Analysis of the early biogenesis of CD1b: involvement of the chaperones calnexin and calreticulin, the proteasome and beta(2)-microglobulin.
beta(2)-Microglobulin (beta(2)m)-associated human CD1b proteins present lipid and glycolipid antigens, which are loaded on CD1b in endosomal compartments. In contrast, the related MHC class I molecules acquire antigenic peptides in the endoplasmic reticulum. Here, we investigated the biogenesis of CD1b before beta(2)m binding in comparison to MHC class I. In beta(2)m-deficient FO-1 cells, we found CD1b heavy chains (HC) complexed with the chaperones calnexin and calreticulin, while MHC class I HC associated only with calnexin. Despite this difference, both CD1b HC and MHC class I HC were degraded when the chaperone interactions were prevented by the glucosidase inhibitor castanospermine. The degradation of both molecules included the proteasome and mannosidases. Chaperone-unassociated CD1b could be rescued from degradation by supplementing FO-1 cells with beta(2)m. Finally, prevention of chaperone interaction significantly reduced neoexpression of CD1b upon differentiation of monocytes to dendritic cells, underlining the importance of chaperones for proper expression of CD1b under physiological conditions.
Hüttinger
R
R
Institute of Immunology, Vienna International Research Cooperation Center at NFI, University of Vienna, Brunner Strasse 59, 1235 Vienna, Austria.
Staffler
G
G
Majdic
O
O
Stockinger
H
H
D015703:Antigens, CD / Q000378:metabolism; D018949:Antigens, CD1 / Q000096:biosynthesis* / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D037281:Calnexin; D037282:Calreticulin; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007212:Indolizines / Q000494:pharmacology; D008361:Mannosidases / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D012261:Ribonucleoproteins / Q000378:metabolism*; D014162:Transfection; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000378:metabolism*; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors; D054836:Indolizidines
D015703:Antigens, CD; D018949:Antigens, CD1; D002135:Calcium-Binding Proteins; D037281:Calnexin; D037282:Calreticulin; D003546:Cysteine Endopeptidases; D015395:Histocompatibility Antigens Class I; D007212:Indolizines; D008361:Mannosidases; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D012261:Ribonucleoproteins; D001613:beta 2-Microglobulin; D001617:beta-Glucosidase; C037806:castanospermine; D054836:Indolizidines