Cutting edge: editing of recycling class II:peptide complexes by HLA-DM.
HLA-DM catalyzes the exchange and selection of ligands for MHC class II molecules within mature endosomal/lysosomal compartments. Here, evidence is provided that DM edits peptides in early endosomes, thus influencing presentation via recycling class II molecules. Maximal class II-restricted presentation of an albumin-derived peptide, dependent on endocytosis and recycling class II molecules, was observed in cells lacking HLA-DM. DM editing of this epitope was observed in early endocytic compartments as shown using inhibitors of early to late endosomal transport. Editing was tempered by coexpression of HLA-DO, suggesting that DM:DO ratio may be important in guiding epitope editing in early endosomal compartments. Thus, HLA-DM appears to interact with, and edit epitopes displayed by, recycling class II molecules.
Pathak
S S
SS
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Lich
J D
JD
Blum
J S
JS
D017951:Antigen Presentation / Q000235:genetics; D002460:Cell Line; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D006681:HLA-D Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D017393:RNA Editing / Q000276:immunology*; D014162:Transfection
D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D010446:Peptide Fragments