Autophagy promotes MHC class II presentation of peptides from intracellular source proteins.
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.
Dengjel
Jörn
J
Department of Immunology, Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
Schoor
Oliver
O
Fischer
Rainer
R
Reich
Michael
M
Kraus
Marianne
M
Müller
Margret
M
Kreymborg
Katharina
K
Altenberend
Florian
F
Brandenburg
Jens
J
Kalbacher
Hubert
H
Brock
Roland
R
Driessen
Christoph
C
Rammensee
Hans-Georg
HG
Stevanovic
Stefan
S
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
D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010455:Peptides; D003546:Cysteine Endopeptidases; C008542:monodansylcadaverine; D002103:Cadaverine