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

Engering, Anneke ; Geijtenbeek, Teunis B H ; van Vliet, Sandra J ; Wijers, Mietske ; van Liempt, Ellis ; Demaurex, Nicolas ; Lanzavecchia, Antonio ; Fransen, Jack ; Figdor, Carl G ; Piguet, Vincent ; van Kooyk, Yvette. / The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. In: Journal of Immunology. 2002 ; Vol. 168, No. 5. pp. 2118-26.
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title = "The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells",
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 Sequence, Antigen Presentation, CD4-Positive T-Lymphocytes/immunology, Cell Adhesion Molecules/metabolism, Cells, Cultured, Clone Cells, Dendritic Cells/cytology, Endocytosis, Endosomes/metabolism, Humans, Lectins/chemistry, Lectins, C-Type, Ligands, Lysosomes/metabolism, Mannose-Binding Lectins, Microscopy, Fluorescence, Molecular Sequence Data, Receptors, Cell Surface/chemistry, Receptors, Immunologic/metabolism, Sequence Homology, Amino Acid",
author = "Anneke Engering and Geijtenbeek, {Teunis B H} and {van Vliet}, {Sandra J} and Mietske Wijers and {van Liempt}, Ellis and Nicolas Demaurex and Antonio Lanzavecchia and Jack Fransen and Figdor, {Carl G} and Vincent Piguet and {van Kooyk}, Yvette",
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month = "3",
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journal = "Journal of Immunology",
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Engering, A, Geijtenbeek, TBH, van Vliet, SJ, Wijers, M, van Liempt, E, Demaurex, N, Lanzavecchia, A, Fransen, J, Figdor, CG, Piguet, V & van Kooyk, Y 2002, 'The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells' Journal of Immunology, vol. 168, no. 5, pp. 2118-26.

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; Demaurex, Nicolas; Lanzavecchia, Antonio; Fransen, Jack; Figdor, Carl G; Piguet, Vincent; van Kooyk, Yvette.

In: Journal of Immunology, Vol. 168, No. 5, 01.03.2002, p. 2118-26.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells

AU - Engering, Anneke

AU - Geijtenbeek, Teunis B H

AU - van Vliet, Sandra J

AU - Wijers, Mietske

AU - van Liempt, Ellis

AU - Demaurex, Nicolas

AU - Lanzavecchia, Antonio

AU - Fransen, Jack

AU - Figdor, Carl G

AU - Piguet, Vincent

AU - van Kooyk, Yvette

PY - 2002/3/1

Y1 - 2002/3/1

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Antigen Presentation

KW - CD4-Positive T-Lymphocytes/immunology

KW - Cell Adhesion Molecules/metabolism

KW - Cells, Cultured

KW - Clone Cells

KW - Dendritic Cells/cytology

KW - Endocytosis

KW - Endosomes/metabolism

KW - Humans

KW - Lectins/chemistry

KW - Lectins, C-Type

KW - Ligands

KW - Lysosomes/metabolism

KW - Mannose-Binding Lectins

KW - Microscopy, Fluorescence

KW - Molecular Sequence Data

KW - Receptors, Cell Surface/chemistry

KW - Receptors, Immunologic/metabolism

KW - Sequence Homology, Amino Acid

M3 - Article

VL - 168

SP - 2118

EP - 2126

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -