The impact of the non-classical MHC proteins HLA-DM and HLA-DO on loading of MHC class II molecules.
Peptide binding to classical major histocompatibility complex (MHC) class II molecules is known to be determined by the properties of the class II peptide binding groove but recently it turned out to be co-controlled by the activity of the non-classical MHC molecules HLA-DM and HLA-DO: HLA-DM functions as a mediator of peptide exchange. In addition, HLA-DM is a chaperone for MHC class II molecules in endosomal and lysosomal loading compartments because it stabilizes the empty MHC class II peptide binding groove and keeps it receptive for peptide loading until appropriate peptide ligands are captured. Since HLA-DM favors the generation of high-stability peptide-MHC class II complexes by releasing low-stability peptide ligands, DM activity affects the peptide repertoire presented on the cell surface of antigen-presenting cells. HLA-DO is expressed mainly in B cells and binds tightly to HLA-DM thereby modulating its activity. Together, HLA-DM and HLA-DO are critical factors in shaping the MHC class II-associated self or foreign peptide repertoire of antigen presenting cells and, hence, govern initiation or prevention of an immune response.
Kropshofer
H
H
Department of Molecular Immunology, German Cancer Research Center, Heidelberg, Germany.
Hämmerling
G J
GJ
Vogt
A B
AB
D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology
C416186:H-2O antigen; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D000949:Histocompatibility Antigens Class II; D018832:Molecular Chaperones; D010455:Peptides