The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells.
Publication year
2002Source
Journal of Immunology, 168, 5, (2002), pp. 2118-26ISSN
Publication type
Article / Letter to editor
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Organization
Tumorimmunology
Cell Biology (UMC)
Journal title
Journal of Immunology
Volume
vol. 168
Issue
iss. 5
Page start
p. 2118
Page end
p. 26
Subject
Routing of proteins in polarized cells; Tumorimmunology; Haematology; Routing van eiwitten in gepolariseerde cellenAbstract
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.
This item appears in the following Collection(s)
- Academic publications [238441]
- Faculty of Medical Sciences [90373]
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