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
Original language | English |
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Pages (from-to) | 2118-2126 |
Number of pages | 9 |
Journal | Journal of immunology (Baltimore, Md. |
Volume | 168 |
Issue number | 5 |
DOIs | |
Publication status | Published - 1 Mar 2002 |
Keywords
- Amino Acid Sequence
- Antigen Presentation
- CD4-Positive T-Lymphocytes/immunology
- Cell Adhesion Molecules/metabolism
- Cells, Cultured
- Clone Cells
- Dendritic Cells/cytology
- Endocytosis
- Endosomes/metabolism
- Humans
- Lectins, C-Type
- Lectins/chemistry
- Ligands
- Lysosomes/metabolism
- Mannose-Binding Lectins
- Microscopy, Fluorescence
- Molecular Sequence Data
- Receptors, Cell Surface/chemistry
- Receptors, Immunologic/metabolism
- Sequence Homology, Amino Acid