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

Anneke Engering, Teunis B H Geijtenbeek, Sandra J van Vliet, Mietske Wijers, Ellis van Liempt, Nicolas Demaurex, Antonio Lanzavecchia, Jack Fransen, Carl G Figdor, Vincent Piguet, Yvette van Kooyk

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)2118-26
Number of pages9
JournalJournal of Immunology
Volume168
Issue number5
Publication statusPublished - 1 Mar 2002

Cite this