H. Kropshofer et al., A ROLE FOR HLA-DO AS A CO-CHAPERONE OF HLA-DM IN PEPTIDE LOADING OF MHC CLASS-II MOLECULES, EMBO journal, 17(11), 1998, pp. 2971-2981
In B cells, the non-classical human leukocyte antigens HLA-DO (DO) and
HLA-DM (DM) are residents of lysosome-like organelles where they form
tight complexes. DM catalyzes the removal of invariant chain-derived
CLIP peptides from classical major histocompatibility complex (MHC) cl
ass II molecules, chaperones them until peptides are available for loa
ding, and functions as a peptide editor. Here we show that DO preferen
tially promotes loading of MHC class II molecules that are dependent o
n the chaperone activity of DMI, and influences editing in a positive
way for some peptides and negatively for others. In acidic compartment
s, DO is engaged in DR-DM-DO complexes whose physiological relevance i
s indicated by the observation that at lysosomal pH DM-DO stabilizes e
mpty class II molecules more efficiently than DM alone. Moreover, expr
ession of DO in a melanoma cell line favors loading of high-stability
peptides. Thus, DO appears to act as a co-chaperone of DM, thereby con
trolling the quality of antigenic peptides to be presented on the cell
surface.