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. 1998 Jun 1;17(11):2971–2981. doi: 10.1093/emboj/17.11.2971

A role for HLA-DO as a co-chaperone of HLA-DM in peptide loading of MHC class II molecules.

H Kropshofer 1, A B Vogt 1, C Thery 1, E A Armandola 1, B C Li 1, G Moldenhauer 1, S Amigorena 1, G J Hämmerling 1
PMCID: PMC1170637  PMID: 9606180

Abstract

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) class II molecules, chaperones them until peptides are available for loading, and functions as a peptide editor. Here we show that DO preferentially promotes loading of MHC class II molecules that are dependent on the chaperone activity of DM, and influences editing in a positive way for some peptides and negatively for others. In acidic compartments, DO is engaged in DR-DM-DO complexes whose physiological relevance is indicated by the observation that at lysosomal pH DM-DO stabilizes empty class II molecules more efficiently than DM alone. Moreover, expression 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 controlling the quality of antigenic peptides to be presented on the cell surface.

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Selected References

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