The monoclonal antibody DCGM4 recognizes Langerin, a protein specific of Langerhans cells, and is rapidly internalized from the cell surface

Valladeau, Jenny; Duvert-Frances, Valérie; Pin, Jean-Jacques; Dezutter‐Dambuyant, Colette; Vincent, Claude; Massacrier, Catherine; Vincent, Jérôme; Yoneda, Kozo; Banchereau, Jacques; Caux, Christophe; Davoust, Jean; Saeland, Sem

doi:10.1002/(sici)1521-4141(199909)29:09<2695::aid-immu2695>3.0.co;2-q

Cited by 245 publications

(165 citation statements)

References 25 publications

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“…In agreement with previous reports, Langerin expression could not be detected in tonsil ( Fig. 1) (11).…”

Section: Dc-sign and The Other C-type Lectins Langerin Mr And Dec-2supporting

confidence: 93%

“…However, the number of CRDs present in these lectins differs and the complexity of the mannose groups that they recognize is distinct (9,10). Langerin contains a single CRD and functions on skin epidermal Langerhans cells (LCs) as an endocytic receptor that is associated with and induces formation of Birbeck granules (11,12). The MR, highly expressed on immature DCs and macrophages, has eight potential CRDs, of which two were shown to be functional for binding end-standing mannose groups on a variety of pathogens and Ags, illustrating its role in innate immunity (13,14).…”

Section: The Dendritic Cell-specific Adhesion Receptor Dc-sign Internmentioning

confidence: 99%

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The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

Engering¹,

Geijtenbeek²,

Vliet³

et al. 2002

The Journal of Immunology

569

500

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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.

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“…In agreement with previous reports, Langerin expression could not be detected in tonsil ( Fig. 1) (11).…”

Section: Dc-sign and The Other C-type Lectins Langerin Mr And Dec-2supporting

confidence: 93%

Section: The Dendritic Cell-specific Adhesion Receptor Dc-sign Internmentioning

confidence: 99%

The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

Engering¹,

Geijtenbeek²,

Vliet³

et al. 2002

The Journal of Immunology

569

500

View full text Add to dashboard Cite

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“…Hence, we next investigated whether Langerin, which is already known to endocytose in LCs (Valladeau et al, 1999(Valladeau et al, , 2000, cycles through the early endosomal pathway in a similar manner to CD1a molecules.…”

Section: Molecular Biology Of the Cell 320mentioning

confidence: 99%

“…Mouse monoclonal antibodies (mAbs) were as follows: anti-lag (IgG1, recognizing an intracellular epitope of Langerin; kindly provided by Dr. Sadao Imamura, Kyoto University, Sakyo-ku, Kyoto, Japan) (Kashihara et al, 1986;Valladeau et al, 2000), DCGM4 (IgG1, recognizing an extracellular epitope of Langerin; Immunotech, Marseille, France) (Valladeau et al, 1999), L243 (IgG2a, anti-DR␣␤ dimmers; BD Biosciences, San Jose, CA), fluorescein isothiocyanate (FITC)-conjugated H1149 (IgG1, anti-CD1a; BD PharMingen, San Diego, CA), H5C6 (IgG1, anti-CD63; kindly provided by Dr. François Lanza, EFS-Alsace, Strasbourg), tetramethylrhodamine B isothiocyanate (TRITC)-conjugated Phalloidin (Sigma, St. Louis, MO), and H4B4 (IgG1, anti-Lamp-2 [CD107b], BD PharMingen). Rabbit anti-EEA1 antiserum (Simonsen et al, 1998) was a generous gift of Dr. Harald Steinmark, (EMBL, Heidelberg, Germany).…”

Section: Antibodies and Reagentsmentioning

confidence: 99%

Birbeck Granules Are Subdomains of Endosomal Recycling Compartment in Human Epidermal Langerhans Cells, Which Form Where Langerin Accumulates

Dermott

Ziylan

Spehner

et al. 2002

MBoC

166

156

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Birbeck granules are unusual rod-shaped structures specific to epidermal Langerhans cells, whose origin and function remain undetermined. We investigated the intracellular location and fate of Langerin, a protein implicated in Birbeck granule biogenesis, in human epidermal Langerhans cells. In the steady state, Langerin is predominantly found in the endosomal recycling compartment and in Birbeck granules. Langerin internalizes by classical receptor-mediated endocytosis and the first Birbeck granules accessible to endocytosed Langerin are those connected to recycling endosomes in the pericentriolar area, where Langerin accumulates. Drug-induced inhibition of endocytosis results in the appearance of abundant open-ended Birbeck granule-like structures appended to the plasma membrane, whereas inhibition of recycling induces Birbeck granules to merge with a tubular endosomal network. In mature Langerhans cells, Langerin traffic is abolished and the loss of internal Langerin is associated with a concomitant depletion of Birbeck granules. Our results demonstrate an exchange of Langerin between early endosomal compartments and the plasma membrane, with dynamic retention in the endosomal recycling compartment. They show that Birbeck granules are not endocytotic structures, rather they are subdomains of the endosomal recycling compartment that form where Langerin accumulates. Finally, our results implicate ADP-ribosylation factor proteins in Langerin trafficking and the exchange between Birbeck granules and other endosomal membranes. INTRODUCTIONLangerhans cells (LCs), the representatives of the dendritic cell lineage in the epidermis and mucosal tissues, capture antigen in the skin before migrating to the T-cell-dependent areas of draining lymph nodes. During this migration, they undergo a maturation process that allows them to present antigens to naive T cells (Kripke et al., 1990;Moll et al., 1993). Notably, Langerhans cells are the only epidermal cells to constitutively express major histocompatibility complex class II molecules (Klareskog et al., 1977;Rowden et al., 1977), CD1a molecules (Fithian et al., 1981), and Langerin (Valladeau et al., 2000) at their cell surface. In addition, Langerhans cells differ ultrastructurally from other dendritic cells through the presence of Birbeck granules (BGs), distinctive rod-shaped structures of variable length with a central, periodically striated lamella (Birbeck et al., 1961).Despite the use of "dynamic" electron microscope studies (reviewed in Schuler et al., 1991), Birbeck granules remain enigmatic. Specifically, conflicting theories exist regarding Article published online ahead of print. Mol. Biol. Cell 10.1091/ mbc.01-06-0300. Article and publication date are at www.molbiolcell.org/cgi/doi/10.1091/mbc.01-06-0300.† These authors contributed equally to this work and are listed in alphabetical order. # Corresponding author. E-mail address: daniel.hanau@efs-alsace.fr. Abbreviations used: Au, gold-labeled; BG, Birbeck granule; ERC, endosomal recycling compartment; Fi, freshl...

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“…Recently, the 5 0 untranslated region of DC-STAMP gene was successfully used in lentiviral vectors yielding long-term and cell-selective transgene expression in vivo. 13 In order to develop additional vectors for permissive expression in DCs in vitro and in vivo with protein, the promoters of the murine genes encoding cd11c, dc-sign, 22 dc-stamp 23 and langerin 24 were cloned. We demonstrated that the DNA sequences that we cloned were primarily active in the DC cell lines, D1, and differentiated Raw 264.7 cells.…”

Section: Introductionmentioning

confidence: 99%

Targeting dendritic cells with antigen via dendritic cell-associated promoters

et al. 2012

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The induction of tumor-specific immune responses is largely dependent on the ability of dendritic cells (DCs) to present tumor-associated antigens to T lymphocytes. Therefore, we investigated the use of DC-associated promoter-driven genetic vaccines to specifically target DC in vivo. Restricted expression of vaccine-encoding genes in DC should enhance specificity and improves their safety for clinical applications. Hereto, 3 --5 kb upstream sequences of the murine genes encoding CD11c, DC-SIGN, DC-STAMP and Langerin were isolated, characterized and subcloned into enhanced green fluorescent protein (EGFP) reporter constructs. Upon electroporation, EGFP was expressed in DC cell lines, but not in other cell lines, confirming DCrestricted promoter activity. When these promoters were cloned into a construct upstream of the gene for ovalbumin (OVA), it appeared that DC-STAMP promoter-driven expression of OVA (pDCSTAMP/OVA) in DC yielded the most efficient OVA-specific CD4 þ and CD8 þ T-cell responses in vitro. Administration of pDC-STAMP/OVA in vivo, using the tattoo gun vaccination system, evoked specific immune responses as evidenced in a mouse tumor model. Adoptively transferred pDC-STAMP/OVA-transfected DCs induced strong CD8 þ T-cell proliferation in vivo. These experiments demonstrate that our DC-directed promoter constructs are potential tools to restrict antigen expression in DC and could be implemented to modulate DC function by the introduction of relevant proteins.

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The monoclonal antibody DCGM4 recognizes Langerin, a protein specific of Langerhans cells, and is rapidly internalized from the cell surface

Cited by 245 publications

References 25 publications

The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

Birbeck Granules Are Subdomains of Endosomal Recycling Compartment in Human Epidermal Langerhans Cells, Which Form Where Langerin Accumulates

Targeting dendritic cells with antigen via dendritic cell-associated promoters

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