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  • The EMBO Journal (1998) 17, 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

Harald Kropshofer1,3, Anne B. Vogt1,3, Clotilde Thery2,3, Elena A. Armandola1,3, Bi-Chen Li1, Gerhard Moldenhauer1, Sebastian Amigorena2 and Günter J. Hämmerling1

  1. German Cancer Research Center, Department of Molecular Immunology, D-69120 Heidelberg, Germany
  2. Institute Curie, F-75005 Paris, France
  3. H.Kropshofer, A.B.Vogt, C.Thery and E.A.Armandola contributed equally to this work

Correspondence to:

Harald Kropshofer, E-mail: a.vogt@dkfz-heidelberg.de

Received 19 February 1998; Accepted 30 March 1998; Revised 30 March 1998

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.

  • Keywords:

    • antigen presentation,
    • chaperone,
    • editing,
    • HLA-DR,
    • peptide binding