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CpG-DNA aided cross-presentation of soluble antigens by dendritic cells


Maurer, T; Heit, A; Hochrein, H; Ampenberger, F; O'Keeffe, M; Bauer, S; Lipford, GB; Vabulas, RM; Wagner, H
2002-08
EUROPEAN JOURNAL OF IMMUNOLOGY
Journal Article
32
8
2356-2364
For cross-presentation immature dendritic cells (DC) require enhanced antigen (Ag) uptake and a maturation signal to prime for MHC class I-restricted CTL responses in vivo. While immunostimulatory CpG-DNA provides, via TLR9, the maturation signal, CpG-DNA linked to Ag augments cellular Ag uptake. In this study we show that CpG-DNA ovalbumin (OVA) conjugates trigger in vivo peptide-specific CTL responses at tenfold lower Ag doses compared to a mixture of CpG-DNA plus OVA. We provide evidence that CpG-DNA-OVA conjugates shift OVA uptake by immature DC from the presumably inefficient fluid phase pinocytosis to efficient DNA receptor-mediated endocytosis. Since the DNA-binding receptor mediating endocytosis lacks any sequence specificity, cellular uptake of OVA conjugated with either stimulatory or non-stimulatory oligonucleotides (ODN) is equally enhanced. As a consequence cross-linking of OVA with either stimulatory or non-stimulatory DNA yields, via enhanced OVA uptake, efficient generation and presentation of the dominant OVA-CTL epitope SIINFEKL. However, only stimulatory CpG-ODN cross-linked to OVA provide the DC maturation signal required to trigger robust primary CTL responses towards the cross-presented MHC class I complexed T cell epitope SIINFEKL. Our studies show that stimulatory CpG-ODN linked to Ag fulfill a dual role: enhancement of Ag uptake yielding efficient Ag cross-presentation by DC and in addition, their activation into professional DC.
WILEY-V C H VERLAG GMBH
CLASS-I MOLECULES; MHC CLASS-I; BACTERIAL-DNA; IMMUNOSTIMULATORY DNA; EXOGENOUS ANTIGENS; PRESENTING CELLS; ACTIVATION; RESPONSES; CYTOKINES; RECEPTOR
10.1002/1521-4141(200208)32:8<2356::AID-IMMU2356>3.0.CO;2-Z
Refer to copyright notice on published article.

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Creation Date 2002-08-01 12:00:00