title: Early endosomal maturation of MHC class II molecules independently of cysteine proteases and H-2DM.
abstract: Major histocompatibility complex (MHC) class II molecules bind and present to CD4(+) T cells peptides derived from endocytosed antigens. Class II molecules associate in the endoplasmic reticulum with invariant chain (Ii), which (i) mediates the delivery of the class II-Ii complexes into the endocytic compartments where the antigenic peptides are generated; and (ii) blocks the peptide-binding site of the class II molecules until they reach their destination. Once there, Ii must be removed to allow peptide binding. The bulk of Ii-class II complexes reach late endocytic compartments where Ii is eliminated in a reaction in which the cysteine protease cathepsin S and the accessory molecule H-2DM play an essential role. Here, we here show that Ii is also eliminated in early endosomal compartments without the intervention of cysteine proteases or H-2DM. The Ii-free class II molecules generated by this alternative mechanism first bind high molecular weight polypeptides and then mature into peptide-loaded complexes.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Villadangos
authors.forename: C
authors.initials: C
authors.lastname: Driessen
authors.forename: G P
authors.initials: GP
authors.lastname: Shi
authors.forename: H A
authors.initials: HA
authors.lastname: Chapman
authors.forename: H L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001692:Biological Transport / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism; D011992:Endosomes / Q000276:immunology* / Q000378:metabolism; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D003546:Cysteine Endopeptidases