Publikation

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

Wissenschaftlicher Artikel/Review - 01.11.2005

Bereiche
PubMed

Zitation
Burster T, Overkleeft H, Weber E, Häring H, Kalbacher H, Kraus M, Reich M, Weissert R, Schnorrer P, Tolosa E, Beck A, Driessen C. Differential processing of autoantigens in lysosomes from human monocyte-derived and peripheral blood dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 2005; 175:5940-9.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Journal of immunology (Baltimore, Md. : 1950) 2005; 175
Veröffentlichungsdatum
01.11.2005
ISSN (Druck)
0022-1767
Seiten
5940-9
Kurzbeschreibung/Zielsetzung

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.