title: HLA-DM acts as a molecular chaperone and rescues empty HLA-DR molecules at lysosomal pH.
abstract: HLA-DM (DM) is a nonclassical MHC class II molecule that interacts with classical MHC II molecules in acidic compartments. During this association DM is supposed to catalyze the release of invariant chain (Ii)-derived CLIP peptides, as well as other peptides bound with low kinetic stability. Here we provide evidence that in lysosomal compartments of B cells a considerable fraction of DM is stably associated with empty DR alphabeta dimers, thereby preventing their functional inactivation and aggregation. Upon encounter with cognate peptide, the DM-associated DR molecules can be rapidly loaded and no longer bind to DM. Thus, DM seems to act as a dedicated class II-specific chaperone. In view of the suggested shortage of DM-resistant self-peptides in the loading compartment, empty class II molecules that are chaperoned by DM may enable the antigen-processing system to respond promptly to the challenge by newly entering antigens.
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kropshofer
authors.forename: S O
authors.initials: SO
authors.lastname: Arndt
authors.forename: G
authors.initials: G
authors.lastname: Moldenhauer
authors.forename: G J
authors.initials: GJ
authors.lastname: Hämmerling
authors.forename: A B
authors.initials: AB
authors.lastname: Vogt
mesh_terms: D000483:Alleles; D001402:B-Lymphocytes; D001692:Biological Transport / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D002451:Cell Compartmentation / Q000276:immunology; D002461:Cell Line, Transformed; D006681:HLA-D Antigens / Q000378:metabolism / Q000502:physiology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000276:immunology* / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D018832:Molecular Chaperones