Differential processing of autoantigens in lysosomes from human monocyte-derived and peripheral blood dendritic cells

Timo Burster, Alexander Beck, Eva Tolosa, Petra Schnorrer, Robert Weissert, Michael Reich, Marianne Kraus, Hubert Kalbacher, Hans-Ulrich Häring, Ekkehard Weber, Herman Overkleeft, Christoph Driessen

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Dendritic cells (DC) initiate immunity and maintain tolerance. Although in vitro-generated DC, usually derived from peripheral blood monocytes (MO-DC), serve as prototype DC to analyze the biology and biochemistry of DC, phenotypically distinct primary types of DC, including CD1c-DC, are present in peripheral blood (PB-DC). The composition of lysosomal proteases in PB-DC and the way their MHC class II-associated Ag-processing machinery handles a clinically relevant Ag are unknown. We show that CD1c-DC lack significant amounts of active cathepsins (Cat) S, L, and B as well as the asparagine-specific endopeptidase, the major enzymes believed to mediate MHC class II-associated Ag processing. However, at a functional level, lysosomal extracts from CD1c-DC processed the multiple sclerosis-associated autoantigens myelin basic protein and myelin oligodendrocyte glycoprotein in vitro more effectively than MO-DC. Although processing was dominated by CatS, CatD, and asparagine-specific endopeptidase in MO-DC, it was dominated by CatG in CD1c-DC. Thus, human MO-DC and PB-DC significantly differ with respect to their repertoire of active endocytic proteases, so that both proteolytic machineries process a given autoantigen via different proteolytic pathways.

Original languageEnglish
Pages (from-to)5940-9
Number of pages10
JournalJournal of Immunology
Volume175
Issue number9
Publication statusPublished - Nov 1 2005
Externally publishedYes

Keywords

  • Antigen Presentation
  • Antigens, CD1
  • Autoantigens
  • Cathepsins
  • Dendritic Cells
  • Endocytosis
  • Glycoproteins
  • Humans
  • Lysosomes
  • Monocytes
  • Myelin Basic Protein
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • RNA, Messenger
  • Journal Article
  • Research Support, Non-U.S. Gov't

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