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The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells

Engering, Anneke
Geijtenbeek, Teunis B H
van Vliet, Sandra J
Wijers, Mietske
van Liempt, Ellis
Lanzavecchia, Antonio
Fransen, Jack
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Published in Journal of Immunology. 2002, vol. 168, no. 5, p. 2118-26
Abstract Dendritic cells (DCs) capture Ags or viruses in peripheral tissue to transport them to lymphoid organs to induce cellular T cell responses. Recently, a DC-specific C-type lectin was identified, DC-specific ICAM-grabbing non-integrin (DC-SIGN), that functions as cell adhesion receptor mediating both DC migration and T cell activation. DC-SIGN also functions as an HIV-1R that captures HIVgp120 and facilitates DC-induced HIV transmission of T cells. Internalization motifs in the cytoplasmic tail of DC-SIGN hint to a function of DC-SIGN as endocytic receptor. In this study we demonstrate that on DCs DC-SIGN is rapidly internalized upon binding of soluble ligand. Mutating a putative internalization motif in the cytoplasmic tail reduces ligand-induced internalization. Detailed analysis using ratio fluorescence imaging and electron microscopy showed that DC-SIGN-ligand complexes are targeted to late endosomes/lysosomes. Moreover, ligands internalized by DC-SIGN are efficiently processed and presented to CD4+ T cells. The distinct pattern of expression of C-type lectins on DCs in situ and their nonoverlapping Ag recognition profile hint to selective functions of these receptors to allow a DC to recognize a wide variety of Ags and to process these to induce T cell activation. These data point to a novel function of the adhesion receptor DC-SIGN as an efficient DC-specific Ag receptor that can be used as a target to induce viral and antitumor immunity.
Keywords Amino Acid SequenceAntigen PresentationCD4-Positive T-Lymphocytes/immunologyCell Adhesion Molecules/metabolism/physiologyCells, CulturedClone CellsDendritic Cells/cytology/immunology/ultrastructureEndocytosisEndosomes/metabolism/ultrastructureHumansLectins/chemistry/metabolism/physiologyLectins, C-TypeLigandsLysosomes/metabolism/ultrastructureMannose-Binding LectinsMicroscopy, FluorescenceMolecular Sequence DataReceptors, Cell Surface/chemistry/metabolism/physiologyReceptors, Immunologic/metabolism/physiologySequence Homology, Amino Acid
PMID: 11859097
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Research group Signaux intracellulaires (210)
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ENGERING, Anneke et al. The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. In: Journal of Immunology, 2002, vol. 168, n° 5, p. 2118-26. doi: 10.4049/jimmunol.168.5.2118 https://archive-ouverte.unige.ch/unige:30344

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Deposited on : 2013-10-11

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