title: Autophagy promotes MHC class II presentation of peptides from intracellular source proteins.
abstract: MHC-peptide complexes mediate key functions in adaptive immunity. In a classical view, MHC-I molecules present peptides from intracellular source proteins, whereas MHC-II molecules present antigenic peptides from exogenous and membrane proteins. Nevertheless, substantial crosstalk between these two pathways has been observed. We investigated the influence of autophagy on the MHC-II ligandome and demonstrated that peptide presentation is altered considerably upon induction of autophagy. The presentation of peptides from intracellular and lysosomal source proteins was strongly increased on MHC-II in contrast with peptides from membrane and secreted proteins. In addition, autophagy influenced the MHC-II antigen-processing machinery. Our study illustrates a profound influence of autophagy on the class II peptide repertoire and suggests that this finding has implications for the regulation of CD4(+) T cell-mediated processes.
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Dengjel
authors.forename: Oliver
authors.initials: O
authors.lastname: Schoor
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
authors.forename: Michael
authors.initials: M
authors.lastname: Reich
authors.forename: Marianne
authors.initials: M
authors.lastname: Kraus
authors.forename: Margret
authors.initials: M
authors.lastname: Müller
authors.forename: Katharina
authors.initials: K
authors.lastname: Kreymborg
authors.forename: Florian
authors.initials: F
authors.lastname: Altenberend
authors.forename: Jens
authors.initials: J
authors.lastname: Brandenburg
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.forename: Roland
authors.initials: R
authors.lastname: Brock
authors.forename: Christoph
authors.initials: C
authors.lastname: Driessen
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D001343:Autophagy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002103:Cadaverine / Q000031:analogs & derivatives*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010455:Peptides; D003546:Cysteine Endopeptidases; C008542:monodansylcadaverine; D002103:Cadaverine