title: Immunogenic peptides bind to class II MHC molecules in an early lysosomal compartment.
abstract: Exogenous protein Ag are processed within endocytic compartments to produce peptides that bind to class II MHC (MHC-II) molecules for presentation to T cells. We have now identified a subcellular compartment in which immunogenic peptides bind to MHC-II as a subset of high density lysosomes. Immunoelectron microscopy of whole cells and dense Percoll gradient subcellular fractions showed early tubulovesicular lysosomes with high levels of MHC-II. Typical mature lysosomes contained less MHC-II. Pulse-chase biosynthetic labeling of macrophages followed by immunoprecipitation of MHC-II from dense lysosomal fractions showed that MHC-II molecules targeted efficiently to lysosomes after biosynthesis. Moreover, lysosomal MHC-II molecules were rapidly loaded with immunogenic peptide (as detected by T cells) soon after exposure of macrophages to Ag and before similar expression of peptide-MHC-II complexes on the plasma membrane; this loading was blocked at 18 degrees C. We propose that nascent MHC-II molecules target to early tubulovesicular lysosomes and bind immunogenic peptides therein; the resulting peptide-MHC-II complexes are then transported to the plasma membrane.
authors.affiliation: Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
authors.forename: C V
authors.initials: CV
authors.lastname: Harding
authors.forename: H J
authors.initials: HJ
authors.lastname: Geuze
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001692:Biological Transport; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D016253:Microscopy, Immunoelectron; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D010455:Peptides