title: Cutting edge: HLA-DO impairs the incorporation of HLA-DM into exosomes.
abstract: In multivesicular bodies, HLA-DM (DM) assists the loading of antigenic peptides on classical MHC class II molecules such as HLA-DR. In cells expressing HLA-DO (DO), DM is redistributed from the internal vesicles to the limiting membrane of these organelles. This suggests that DO might reduce DM incorporation into exosomes, which are shed upon fusion of multivesicular bodies with the plasma membrane. To test this hypothesis, we used the 721.45 B lymphoblastoid cell line and different HeLa cell transfectants. We demonstrate that the poor recovery of DM in exosomes as compared with HLA-DR is not the mere reflection of differences in protein expression. Indeed, we found that DO contributes to the inefficient transfer of DM to exosomes. This negative regulation requires an intact di-leucine endosomal sorting motif in the cytoplasmic tail of HLA-DOβ. These results demonstrate that canonical sorting signals and protein-protein interactions modulate the selection of MHC protein cargos.
authors.affiliation: Laboratoire d'Immunologie Moléculaire, Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
authors.forename: Fangming
authors.initials: F
authors.lastname: Xiu
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Côté
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Bourgeois-Daigneault
authors.forename: Alexandre
authors.initials: A
authors.lastname: Brunet
authors.forename: Marie-Élaine
authors.initials: MÉ
authors.lastname: Gauvreau
authors.forename: Andrew
authors.initials: A
authors.lastname: Shaw
authors.forename: Jacques
authors.initials: J
authors.lastname: Thibodeau
mesh_terms: D020816:Amino Acid Motifs; D055354:Exosomes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport / Q000235:genetics / Q000276:immunology
chemical_list: D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens