title: MHC class II antigen presentation by dendritic cells regulated through endosomal sorting.
abstract: For the initiation of adaptive immune responses, dendritic cells present antigenic peptides in association with major histocompatibility complex class II (MHCII) to naïve CD4(+) T lymphocytes. In this review, we discuss how antigen presentation is regulated through intracellular processing and trafficking of MHCII. Newly synthesized MHCII is chaperoned by the invariant chain to endosomes, where peptides from endocytosed pathogens can bind. In nonactivated dendritic cells, peptide-loaded MHCII is ubiquitinated and consequently sorted by the ESCRT machinery to intraluminal vesicles of multivesicular bodies, ultimately leading to lysosomal degradation. Ubiquitination of newly synthesized MHCII is blocked when dendritic cells are activated, now allowing its transfer to the cell surface. This mode of regulation for MHCII is a prime example of how molecular processing and sorting at multivesicular bodies can determine the expression of signaling receptors at the plasma membrane.
authors.affiliation: Utrecht University, Faculty of Veterinary Medicine, Department of Biochemistry and Cell Biology, Yalelaan 2, 3584 CM, Utrecht, The Netherlands.
authors.forename: Toine
authors.initials: T
authors.lastname: ten Broeke
authors.forename: Richard
authors.initials: R
authors.lastname: Wubbolts
authors.forename: Willem
authors.initials: W
authors.lastname: Stoorvogel
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000276:immunology; D011992:Endosomes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008247:Lysosomes / Q000276:immunology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D056827:Endosomal Sorting Complexes Required for Transport; D000949:Histocompatibility Antigens Class II; C045084:invariant chain