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 journalArticle

40 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

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Autoantigens
Lysosomes
Dendritic Cells
Monocytes
Blood Cells
Endopeptidases
cathepsin S
Asparagine
Myelin-Oligodendrocyte Glycoprotein
Cathepsin L
Cathepsin B
Myelin Basic Protein
Biochemistry
Multiple Sclerosis

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

Cite this

Burster, T., Beck, A., Tolosa, E., Schnorrer, P., Weissert, R., Reich, M., ... Driessen, C. (2005). Differential processing of autoantigens in lysosomes from human monocyte-derived and peripheral blood dendritic cells. Journal of Immunology, 175(9), 5940-9.

Differential processing of autoantigens in lysosomes from human monocyte-derived and peripheral blood dendritic cells. / Burster, Timo; Beck, Alexander; Tolosa, Eva; Schnorrer, Petra; Weissert, Robert; Reich, Michael; Kraus, Marianne; Kalbacher, Hubert; Häring, Hans-Ulrich; Weber, Ekkehard; Overkleeft, Herman; Driessen, Christoph.

In: Journal of Immunology, Vol. 175, No. 9, 01.11.2005, p. 5940-9.

Research output: Contribution to journalArticle

Burster, T, Beck, A, Tolosa, E, Schnorrer, P, Weissert, R, Reich, M, Kraus, M, Kalbacher, H, Häring, H-U, Weber, E, Overkleeft, H & Driessen, C 2005, 'Differential processing of autoantigens in lysosomes from human monocyte-derived and peripheral blood dendritic cells', Journal of Immunology, vol. 175, no. 9, pp. 5940-9.
Burster, Timo ; Beck, Alexander ; Tolosa, Eva ; Schnorrer, Petra ; Weissert, Robert ; Reich, Michael ; Kraus, Marianne ; Kalbacher, Hubert ; Häring, Hans-Ulrich ; Weber, Ekkehard ; Overkleeft, Herman ; Driessen, Christoph. / Differential processing of autoantigens in lysosomes from human monocyte-derived and peripheral blood dendritic cells. In: Journal of Immunology. 2005 ; Vol. 175, No. 9. pp. 5940-9.
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AU - Beck, Alexander

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AU - Weissert, Robert

AU - Reich, Michael

AU - Kraus, Marianne

AU - Kalbacher, Hubert

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