Autophagy promotes MHC class II presentation of peptides from intracellular source proteins
- Jörn Dengjel†,‡,
- Oliver Schoor†,‡,
- Rainer Fischer§,
- Michael Reich¶,
- Marianne Kraus¶,
- Margret Müller†,
- Katharina Kreymborg†,
- Florian Altenberend†,
- Jens Brandenburg∥,
- Hubert Kalbacher∥,
- Roland Brock§,
- Christoph Driessen¶,
- Hans-Georg Rammensee†, and
- Stefan Stevanovic†,††
- †Department of Immunology and §Department of Molecular Biology, Institute for Cell Biology, ¶Department of Medicine II, and ∥Medical and Natural Sciences Research Center, University of Tübingen, 72076 Tübingen, Germany
-
Edited by Peter Cresswell, Yale University School of Medicine, New Haven, CT, and approved April 7, 2005 (received for review February 11, 2005)
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.
Footnotes
-
↵ †† To whom correspondence should be addressed. E-mail: stefan.stevanovic{at}unituebingen.de.
-
↵ ‡ J.D. and O.S. contributed equally to this work.
-
Author contributions: J.D., O.S., H.K., R.B., C.D., H.-G.R., and S.S. designed research; J.D., O.S., R.F., M.R., M.K., M.M., K.K., F.A., and J.B. performed research; J.D. and O.S. analyzed data; and J.D., O.S., H.-G.R., and S.S. wrote the paper.
-
This paper was submitted directly (Track II) to the PNAS office.
-
Abbreviation: MDC, monodansylcadaverine.
-
Data deposition: The microarray data reported in this paper have been deposited in the Gene Expression Omnibus database (accession no. GSE2435).
-
See Commentary on page 7779.
- Copyright © 2005, The National Academy of Sciences
