Analysis of the early biogenesis of CD1b: involvement of the chaperones calnexin and calreticulin, the proteasome and β2-microglobulin

β2-Microglobulin (β2m)-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 β2m binding in comparison to MHC class I. In β2m-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 β2m. 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.