The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells.
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.
Engering
Anneke
A
Department of Molecular Cell Biology, Vrye Universiteit Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Geijtenbeek
Teunis B H
TB
van Vliet
Sandra J
SJ
Wijers
Mietske
M
van Liempt
Ellis
E
Demaurex
Nicolas
N
Lanzavecchia
Antonio
A
Fransen
Jack
J
Figdor
Carl G
CG
Piguet
Vincent
V
van Kooyk
Yvette
Y
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D002999:Clone Cells; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D037181:Lectins, C-Type; D008024:Ligands; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D011971:Receptors, Immunologic / Q000378:metabolism / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037102:Lectins; D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin