Affinage

CD207

C-type lectin domain family 4 member K · UniProt Q9UJ71

Length
328 aa
Mass
36.7 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD207/Langerin is a type II Ca2+-dependent C-type lectin of Langerhans cells (LCs) that acts as an endocytic pattern-recognition receptor and the architect of Birbeck granules, specialized membrane compartments it generates by inducing membrane superimposition and zippering (PMID:10661407, PMID:11809842). Its extracellular region assembles into a rigid trimer stabilized by a coiled-coil neck, an arrangement required for high-avidity capture of glycoprotein ligands; the trimeric protein binds high-mannose oligosaccharides optimally, and full-length langerin mediates uptake and degradation of mannosylated cargo with pH-dependent release governed by CRD-neck interactions (PMID:12626394, PMID:20181944). Glycan recognition occurs primarily at a single Ca2+-dependent CRD site that accommodates diverse ligands—mannose, GlcNAc, fucose-bearing blood group antigens, beta-glucan, and 6-sulfated galactose—through coordination of vicinal hydroxyls, with lysine residues (Lys-299, Lys-313) forming an extended subsite for sulfated glycans (PMID:20026605, PMID:21112338), while an allosteric intradomain network couples pH to Ca2+ affinity to drive fast cargo release (PMID:27560542). After ligand capture langerin internalizes by receptor-mediated endocytosis and is routed through the Rab11A-positive endosomal recycling compartment, where a Rab11A/Myosin Vb/Rab11-FIP2 platform controls its sorting, recycling and stability; loss of Rab11A missorts langerin to lysosomes and abolishes Birbeck granule biogenesis (PMID:17538027, PMID:22420646, PMID:15191545). Functionally, langerin captures and degrades pathogens—it internalizes HIV-1 into Birbeck granules via caveolin-1-dependent uptake to restrict LC infection and T-cell transmission (PMID:17334373, PMID:25551286), serves as the principal fungal receptor recognizing mannan and beta-glucan (PMID:20097424), discriminates Staphylococcus aureus through beta-GlcNAc on wall teichoic acid to shape proinflammatory cytokine output (PMID:31088921, PMID:33591717), and acts as an entry receptor for influenza A virus through mannose-rich hemagglutinin glycans (PMID:26468543). Langerin also directs antigen handling: routing cargo to early endosomes enhances MHC-I cross-presentation (PMID:26456691), and it contributes to CD1a-restricted presentation of mycobacterial lipids (PMID:14991068). Birbeck granules themselves are dispensable for core LC antigen-presentation functions (PMID:15601833). Natural CRD polymorphisms tune or abrogate function—W264R abolishes sugar binding and Birbeck granule formation, while the linked K313I/N288D variants redirect glycan specificity and destabilize the Ca2+ site (PMID:15816828, PMID:24217250).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Establishing langerin as a distinct, rapidly internalized LC surface molecule defined the protein biochemically and showed its trafficking diverged from classical MHC II antigen-loading routes.

    Evidence Monoclonal antibody generation, immunoprecipitation, internalization and colocalization assays

    PMID:10508244

    Open questions at the time
    • No molecular identity of the internalization route
    • Ligand and function unknown at this stage
  2. 2000 High

    Cloning langerin and demonstrating that its expression alone induces Birbeck granules in fibroblasts established it as both a mannose-binding C-type lectin and the causal driver of these LC-specific organelles.

    Evidence cDNA transfection into fibroblasts, electron microscopy, antibody internalization assay

    PMID:10661407

    Open questions at the time
    • Mechanism of membrane zippering undefined
    • Physiological glycan ligands not mapped
  3. 2002 High

    Showing Birbeck granules are subdomains of the endosomal recycling compartment forming where langerin accumulates placed langerin trafficking within defined endocytic and recycling pathways.

    Evidence Pharmacological inhibition of endocytosis/recycling, immunofluorescence, EM, fractionation in primary human LCs

    PMID:11809842

    Open questions at the time
    • Specific Rab/motor machinery not yet identified
    • ARF involvement only implicated
  4. 2003 High

    Defining the trimeric architecture stabilized by the coiled-coil neck and its requirement for glycoprotein binding linked langerin oligomerization to ligand avidity and pH-dependent release.

    Evidence Analytical ultracentrifugation, circular dichroism, sugar-binding and neoglycoprotein endocytosis assays

    PMID:12626394

    Open questions at the time
    • Atomic structure of the trimer not yet resolved
    • Secondary binding sites not addressed
  5. 2005 High

    Knockout of langerin in mice showed Birbeck granules are dispensable for canonical LC antigen-capture and presentation, separating the organelle-forming role from general LC immune function.

    Evidence Langerin-/- mouse, EM, FACS, MHC I/II antigen presentation assays, in vivo challenge

    PMID:15601833

    Open questions at the time
    • Did not test pathogen-specific capture roles
    • Mouse vs human functional divergence not addressed
  6. 2007 High

    Identifying Rab11A as the master regulator of langerin recycling, stability and Birbeck granule biogenesis connected the receptor to a defined endosomal sorting machinery.

    Evidence Dominant-negative Rab11A, siRNA of Rab11A and RCP/Rip11, immunofluorescence, EM in transfected cells

    PMID:17538027

    Open questions at the time
    • Motor and tethering components not yet defined
    • Sorting signals on langerin not mapped
  7. 2007 High

    Demonstrating that langerin captures and degrades HIV-1 in Birbeck granules to prevent LC infection and transmission established a protective antiviral function for the receptor.

    Evidence Primary human LC HIV-1 infection and transmission assays, anti-langerin blocking antibody

    PMID:17334373

    Open questions at the time
    • Endocytic pathway mediating uptake not yet defined
    • Viral glycan epitope not yet identified
  8. 2009 High

    High-resolution crystal structures of the CRD and trimeric ectodomain revealed three Ca2+-dependent sugar sites 42 Å apart and confirmed high-mannose glycans as optimal ligands, providing the structural basis for multivalent recognition.

    Evidence X-ray crystallography of CRD and trimeric fragment, AUC, glycan array, structure-guided mutagenesis

    PMID:18061677 PMID:19175323 PMID:20181944

    Open questions at the time
    • Existence of a Ca2+-independent second site debated
    • Structural basis of membrane zipping inferred indirectly
  9. 2010 High

    Comprehensive structural and array studies established a single Ca2+-dependent site as the binding hub for diverse glycans (oligomannose, beta-glucan, blood group B, 6-sulfated galactose) and mapped lysine-dependent recognition of sulfated sugars.

    Evidence X-ray crystallography of CRD-ligand complexes, glycoconjugate microarrays, site-directed mutagenesis of Lys-299/Lys-313

    PMID:20026605 PMID:21112338

    Open questions at the time
    • Reconciliation with proposed second site unresolved
    • Physiological relevance of each glycan class not weighted
  10. 2010 High

    Identifying langerin as the primary fungal receptor recognizing mannan and beta-glucan extended its pathogen-sensing role to fungi.

    Evidence Recombinant langerin binding assays, LC-fungal interaction assays, anti-langerin blocking

    PMID:20097424

    Open questions at the time
    • Downstream signaling/effector outcome not characterized
    • In vivo antifungal role not tested
  11. 2012 High

    Live-imaging dissection of a Rab11A/Myosin Vb/Rab11-FIP2 platform showed it acts at two spatially distinct steps—ERC sorting and plasma-membrane docking/fusion—refining the trafficking model for langerin.

    Evidence Live-cell FRET, FRAP, confocal and TIRF microscopy in langerin-expressing cells

    PMID:22420646

    Open questions at the time
    • How langerin cargo selects this platform unknown
    • Link to Birbeck granule membrane curvature unresolved
  12. 2013 High

    Showing that common K313I and linked N288D polymorphisms shift glycan specificity and destabilize the Ca2+ site established natural genetic variation as a tuner of langerin recognition.

    Evidence Mutagenesis, glycan array, X-ray crystallography of polymorphic forms

    PMID:24217250

    Open questions at the time
    • Physiological/clinical consequence of haplotypes untested
    • Effect on pathogen recognition in vivo unknown
  13. 2014 High

    Demonstrating caveolin-1-dependent uptake of CRD-captured HIV-1 trimers into lysosome-linked Birbeck granules defined the endocytic route underlying antiviral restriction.

    Evidence Anti-CRD antibody and soluble trimeric langerin blocking, caveolin-1 siRNA and pharmacological inhibition, HIV integration assay in primary LCs

    PMID:22364686 PMID:25070850 PMID:25551286

    Open questions at the time
    • Relative contribution of clathrin vs caveolin pathways context-dependent
    • Trigger linking caveolar uptake to degradation unresolved
  14. 2015 High

    Establishing that langerin routes antigen to EEA1+ early endosomes to enhance MHC-I cross-presentation defined a distinct antigen-handling fate beyond pathogen degradation.

    Evidence Anti-langerin vs anti-dectin-1 antibody-coupled peptide delivery, EEA1 colocalization, CD8+ T-cell cross-presentation in primary LCs

    PMID:26456691

    Open questions at the time
    • Switch between degradative and cross-presenting routing not defined
    • In vivo vaccine relevance untested
  15. 2015 High

    Identifying langerin as an entry receptor for influenza A virus, requiring internalization and using early endosomes, extended its receptor repertoire and showed glycan capture can promote rather than restrict infection.

    Evidence Lec2 CHO cells expressing langerin or endocytosis-defective mutant, replication assays, pathway inhibitors, endosomal markers

    PMID:26468543

    Open questions at the time
    • Outcome (restriction vs entry) determinants across pathogens unclear
    • Role in primary LCs in vivo not addressed
  16. 2016 High

    NMR and MD analysis revealed an allosteric intradomain network coupling pH to Ca2+ affinity, providing the molecular mechanism for fast endosomal cargo release.

    Evidence NMR spectroscopy, molecular dynamics, site-directed mutagenesis of the CRD

    PMID:27560542

    Open questions at the time
    • Coupling to trafficking machinery not demonstrated
    • Generality across ligand classes untested
  17. 2019 High

    Demonstrating langerin recognition of beta-GlcNAc on S. aureus wall teichoic acid, shaping cytokine responses, showed langerin discriminates bacterial species and tunes inflammation.

    Evidence LC-S. aureus assays, anti-langerin blocking, cytokine measurement, murine epicutaneous model with WTA mutants and human langerin transgene

    PMID:31088921 PMID:33591717

    Open questions at the time
    • Signaling pathway from langerin to cytokine induction undefined
    • Why TarP vs TarS differ despite equal recognition unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how langerin's glycan engagement is mechanistically transduced into downstream signaling and how cargo fate is switched between degradative Birbeck granules and cross-presenting early endosomes.
  • No cytoplasmic signaling effectors identified
  • Switch between degradation and cross-presentation routing undefined
  • Existence/function of a Ca2+-independent secondary glycan site unresolved (#27 vs #12)

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 3 GO:0038024 cargo receptor activity 3 GO:0140299 molecular sensor activity 3 GO:0008289 lipid binding 2
Localization
GO:0005768 endosome 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3 GO:0005764 lysosome 2
Pathway
R-HSA-168256 Immune System 5 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-1643685 Disease 3
Partners
CAV1MYO5BRAB11ARAB11FIP2RCP/RAB11FIP1
Complex memberships
Birbeck granuleLangerin trimer (coiled-coil neck)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Langerin is a type II Ca2+-dependent C-type lectin with mannose-binding specificity, constitutively associated with Birbeck granules, that induces formation of Birbeck granules upon transfection into fibroblasts, demonstrating it is a potent inducer of membrane superimposition and zippering leading to Birbeck granule formation. cDNA transfection into fibroblasts, electron microscopy, antibody internalization assay Immunity High 10661407
1999 Langerin is a 40-kDa cell surface protein (pI 5.2–5.5) that is rapidly internalized at 37°C but does not gain access to MHC class II compartments; it does not colocalize with LAMP-1 lysosomal markers. Monoclonal antibody generation, immunoprecipitation, internalization assay, immunofluorescence colocalization European journal of immunology High 10508244
2002 Birbeck granules are subdomains of the endosomal recycling compartment in human epidermal Langerhans cells that form where Langerin accumulates; Langerin internalizes by classical receptor-mediated endocytosis and first appears in Birbeck granules connected to recycling endosomes in the pericentriolar area. Inhibition of endocytosis produces open-ended Birbeck granule-like structures at the plasma membrane, while inhibition of recycling causes Birbeck granules to merge with a tubular endosomal network. ARF proteins are implicated in Langerin trafficking. Drug inhibition of endocytosis/recycling, immunofluorescence, electron microscopy, subcellular fractionation in primary human LCs Molecular biology of the cell High 11809842
2003 The extracellular region of langerin exists as a stable trimer held together by a coiled-coil of alpha-helices formed by the neck region. The langerin CRD shows specificity for mannose, GlcNAc, and fucose, but only the trimeric extracellular domain binds glycoprotein ligands. Langerin binds mammalian high-mannose oligosaccharides and mannose-containing structures on yeast invertase but not complex glycans. Full-length langerin mediates efficient uptake and degradation of mannosylated neoglycoprotein ligands, with pH-dependent ligand release involving CRD-neck interactions. Analytical ultracentrifugation, circular dichroism spectroscopy, sugar binding assays, transfection of full-length langerin in rat fibroblasts, endocytosis assay with mannosylated neoglycoprotein Glycobiology High 12626394
2004 Langerhans cells utilize langerin to present nonpeptide antigens of Mycobacterium leprae to T cell clones in a CD1a-restricted and langerin-dependent manner; LC-like DCs were more efficient at CD1a-restricted antigen presentation than monocyte-derived DCs. Antigen presentation assay with LC-derived DCs and T cell clones, anti-langerin antibody blocking, freshly isolated epidermal LCs from leprosy patients The Journal of clinical investigation High 14991068
2005 Genetic disruption of langerin abolishes Birbeck granules in Langerhans cells without altering LC numbers, morphology, antigen capture, migration to lymph nodes, phenotypic maturation, OVA presentation on MHC II to CD4+ T cells, or cross-presentation on MHC I to CD8+ T cells. Langerin and Birbeck granules are dispensable for these LC functions. Langerin knockout mouse (langerin-/- on C57BL/6), electron microscopy, FACS, antigen presentation assays, in vivo pathogen challenge Molecular and cellular biology High 15601833
2007 Langerin prevents HIV-1 transmission by Langerhans cells: HIV-1 captured by langerin is internalized into Birbeck granules and degraded. Inhibition of langerin allowed LC infection and subsequent HIV-1 transmission. LCs also inhibited T-cell infection by viral clearance through langerin. Primary human LC HIV-1 infection assays, anti-langerin blocking antibody, T-cell transmission assay, fluorescence microscopy Nature medicine High 17334373
2007 Rab11A controls the biogenesis of Birbeck granules by regulating Langerin recycling and stability; dominant-negative Rab11A or Rab11A depletion causes missorting of Langerin to lysosomal compartments and abrogates BG formation. Loss of Rab11A-interacting protein RCP (but not Rip11) also modestly affects Langerin stability and BG biogenesis. Dominant-negative Rab11A overexpression, siRNA Rab11A depletion, siRNA RCP/Rip11 depletion, immunofluorescence, electron microscopy in Langerin-transfected cells Molecular biology of the cell High 17538027
2007 Crystal structure of the langerin CRD reveals a fold similar to DC-SIGN with two sugar-binding sites: one Ca2+-dependent (conserved in C-type lectins) binding mannose, and a second novel Ca2+-independent site; complexes with mannose and maltose resolved at 1.6 Å and 2.1 Å respectively. X-ray crystallography (apo at 2.5 Å; mannose complex at 1.6 Å; maltose complex at 2.1 Å) of recombinant langerin CRD Molecular immunology High 18061677
2009 Crystal structure of trimeric langerin extracellular fragment at high resolution shows the neck region forms a coiled-coil of alpha-helices; multiple interactions between neck and CRDs create a rigid trimer with three Ca2+-dependent sugar-binding sites separated by 42 Å. High-mannose oligosaccharides are the best trimeric langerin ligands by glycan array screening. X-ray crystallography of trimeric langerin extracellular fragment, analytical ultracentrifugation, glycan array screening The Journal of biological chemistry High 20181944
2009 Crystal structure of the human langerin CRD solved at 1.5 Å; molecular modeling of gp120 high-mannose binding was validated. Truncation and mutagenesis studies in transfected fibroblasts identified the role of the CRD in membrane zipping during Birbeck granule formation, with some contribution from the cytoplasmic domain. X-ray crystallography (1.5 Å), molecular modeling, truncation and point-mutant transfection in fibroblasts, electron microscopy Biochemistry High 19175323
2009 Langerin has dual specificity: outstanding affinity for galactose-6-sulfated oligosaccharides (including keratan sulfate) through an extended binding site, and preserved mannose-binding activity. Mutagenesis identified Lys-299 and Lys-313 as forming the extended binding site for sulfated glycans. Comprehensive glycoconjugate microarray, quantitative frontal affinity chromatography, site-directed mutagenesis of Lys-299 and Lys-313 The Journal of biological chemistry High 20026605
2010 Crystal structures of human langerin CRD bound to oligomannose compounds, blood group B antigen, and a β-glucan fragment reveal that all bind through a single Ca2+-dependent site via coordination of vicinal hydroxyl groups. Oligomannose binds through a single mannose residue; β-glucan (Glcβ1-3Glcβ1-3Glc) binds through a single glucose residue; fucose of blood group B binds Ca2+ site. 6-sulfated galactose coordinates Ca2+ via equatorial 3-OH and axial 4-OH, with salt bridges to two lysine residues. No evidence for a second Ca2+-independent binding site was found in these structural studies. X-ray crystallography of CRD–ligand complexes, bacterial polysaccharide microarray screening Journal of molecular biology High 21112338
2010 Langerin is the primary fungal receptor on Langerhans cells, recognizing both mannan and β-glucan structures on fungal cell walls. Langerin interacts with Candida and Saccharomyces species and Malassezia furfur, but only weakly with Cryptococcus species; anti-langerin antibody blocks LC–fungal interactions. Binding assays with recombinant langerin, LC fungal interaction assays, anti-langerin antibody blocking Molecular immunology High 20097424
2004 The Birbeck granule-inducing mutation W264R in the langerin CRD (substitution of tryptophan by arginine at position 264) abolishes sugar-binding activity of langerin, and heterozygous presence of this mutation in a human is associated with absence of Birbeck granules. Human genetic analysis (heterozygous point mutation), expression of mutant Langerin in fibroblasts, sugar-binding assay The Journal of investigative dermatology High 15816828
2006 SNPs in the langerin CRD reduce affinity for mannose and decrease stability of the extracellular domain; the W264R mutation abolishes sugar-binding activity. All four common langerin haplotypes mediate endocytosis of neoglycoprotein ligands in transfected fibroblasts. Expression of polymorphic full-length langerin in fibroblasts, sugar-binding assays, differential scanning calorimetry on extracellular domain fragments The Journal of biological chemistry High 16567809
2013 A common SNP changing Lys-313 to isoleucine abolishes langerin binding to oligosaccharides with terminal 6SO4-Gal and enhances binding to terminal GlcNAc. This K313I SNP is tightly linked to N288D, which destabilizes the Ca2+-binding site and reduces overall glycan affinity. Mutagenesis, glycan array screening, X-ray crystallography of polymorphic forms The Journal of biological chemistry High 24217250
2002 Mouse langerin protein forms multimers and binds mannan-agarose (Ca2+-dependent mannose binding); expression in fibroblasts induces Birbeck granule-like structures. A point mutation F244L in the CRD transforms BG into cored tubule-like structures in transfectants. Recombinant protein expression, mannan-agarose binding assay, cDNA transfection in fibroblasts, electron microscopy Journal of immunology High 11777972
2004 Mouse langerin, SIGNR1, and SIGNR3 can each be internalized upon cell-surface expression in transfected non-macrophage cells; mLangerin (unlike mDC-SIGN) mediates uptake of FITC-dextran and zymosan, with distinct carbohydrate recognition properties. FITC-dextran uptake by Langerin is blocked by mannan. Transfection of tag-labeled lectins in cell lines, FITC-dextran/zymosan uptake assays, blocking with mannan/EDTA International immunology Medium 15096474
2004 Langerin binds a Lewis X-related sequence with sulfate at position 6 of the terminal galactose as its dominant specificity in carbohydrate array screening, distinguishing it from SIGN-R1 and SIGN-R3 which prefer mannose/fucose structures. Carbohydrate array probing with soluble IgG-Fc chimeras of langerin, SIGN-R1, SIGN-R3; cell-based uptake assays International immunology Medium 15136555
2012 A Rab11A/Myosin Vb/Rab11-FIP2 platform regulates langerin trafficking at two distinct sites: at a sorting site in the endosomal recycling compartment (ERC) where transport vesicles form, and at the late stage of docking/tethering and fusion of langerin recycling vesicles to the plasma membrane. Live-cell FRET, fast FRAP, fast confocal and TIRF microscopy in langerin-expressing cells Traffic High 22420646
2004 Langerin traffic and Birbeck granule formation were reconstituted in a human melanoma cell line (M10-22E) transfected with Langerin; Langerin distributes between the Rab11+ endosomal recycling compartment and the plasma membrane, and drives BG biogenesis in the endosomal recycling compartment. Interruption of endocytosis or recycling redistributes intracellular Langerin and alters BG morphology. Stable transfection of melanoma cells, immunofluorescence, electron microscopy, pharmacological inhibition of endocytosis/recycling The Journal of investigative dermatology High 15191545
2014 Langerin on Langerhans cells captures HIV-1 as surface trimers through its carbohydrate recognition domain (CRD), preferentially binding gp140 and whole HIV particles; both phases of HIV transfer from epidermal LCs to T cells are inhibited by anti-langerin CRD antibody or soluble trimeric langerin extracellular domain, which did not inhibit direct HIV infection of T cells. HIV transfer assays with primary eLCs and Mutz-3 LCs, anti-langerin CRD mAb blocking, soluble trimeric langerin inhibition, cross-linking experiments Journal of immunology High 25070850
2014 Langerin-mediated HIV-1 uptake in primary human LCs is caveolin-1-dependent; langerin and caveolin-1 co-localize at the cell membrane and in vesicles; Birbeck granules are langerin/caveolin-1-positive vesicles linked to the lysosomal degradation pathway. Inhibition of caveolar endocytosis or siRNA silencing of caveolin-1 increases HIV-1 integration and infection; inhibition of clathrin-mediated endocytosis does not affect HIV-1 restriction. Co-localization microscopy, caveolar endocytosis inhibition, caveolin-1 siRNA silencing, clathrin inhibition, HIV-1 integration assay in primary LCs Retrovirology High 25551286
2015 Langerin functions as an authentic receptor mediating attachment and infectious entry of influenza A virus (IAV) via lectin-mediated recognition of mannose-rich glycans on viral hemagglutinin. Endocytosis-defective langerin mutant bound IAV but prevented infection, confirming internalization is required. Langerin-mediated IAV infection is pH- and dynamin-dependent, uses clathrin- and caveolin-mediated endocytic pathways, and utilizes early (Rab5+) but not late (Rab7+) endosomes. Lec2 SIA-deficient CHO cells expressing langerin or endocytosis-defective langerin mutant; viral replication, mRNA transcription, protein synthesis assays; pathway inhibitors; endosomal marker colocalization Journal of virology High 26468543
2019 Human langerin on Langerhans cells directly recognizes Staphylococcus aureus through β-N-acetylglucosamine (GlcNAc) modifications on wall teichoic acid (WTA), discriminating S. aureus from other staphylococci. The S. aureus WTA glycoprofile influences the level of proinflammatory cytokines produced by LCs. In a murine epicutaneous model, S. aureus strongly upregulated Cxcl1, Il6, and Il17, requiring both human langerin and WTA β-GlcNAc. LC-S. aureus interaction assays, anti-langerin antibody blocking, cytokine measurement, murine epicutaneous infection model with human langerin-expressing and WTA-mutant S. aureus strains mBio High 31088921
2021 Langerin specifically recognizes β-GlcNAc (both β1,4 and β1,3 linkages produced by TarS and TarP) but not α1,4-GlcNAc (TarM) on S. aureus WTA; β-GlcNAc is sufficient for langerin binding as demonstrated with chemically synthesized WTA molecules. TarP-modified S. aureus induced increased cytokine production and LC maturation compared to TarS-modified bacteria despite similar langerin recognition. Genetically modified S. aureus strains, in vitro generated LC binding/activation assays, chemically synthesized WTA molecules, cytokine measurements ACS infectious diseases High 33591717
2011 Langerin recognizes glycosaminoglycans (GAGs) through a novel Ca2+-independent binding site distinct from the canonical Ca2+-dependent CRD site; this site is only detectable in the trimeric extracellular domain and is specific for 6-O-sulfation and iduronic acid content rather than net charge. Molecular modeling, surface plasmon resonance-like binding assays, comparison of GAG vs. mannose binding in trimeric vs. monomeric langerin PloS one Medium 23226363
2016 An allosteric intradomain network in the langerin CRD modulates Ca2+ affinity depending on pH, promoting fast ligand release; two loops undergo coupled motions controlling Ca2+ binding/release over multiple time scales. Site-directed mutagenesis confirmed the allosteric network. NMR spectroscopy, molecular dynamics simulations, site-directed mutagenesis of the CRD Journal of the American Chemical Society High 27560542
2016 Human and murine langerin share identical three-dimensional structures and recognize simple ligands identically, but screening >300 bacterial polysaccharides revealed highly diverging avidity and selectivity for large complex glycans; a highly variable surface adjacent to the canonical binding site likely forms a secondary interaction site for large glycans. Bacterial polysaccharide microarray (>300 compounds), X-ray crystallography of murine langerin, structural/evolutionary conservation analysis The Journal of biological chemistry High 27903635
2008 Anti-Langerin antibody targeting of splenic CD8+ DCs in vivo mediates efficient antigen presentation to both CD8+ and CD4+ T cells (4–8 cycles of division in 3 days); peptide–MHC I and II complexes persist for days. CD8+ DCs expressing Langerin are located predominantly in the marginal zone of mouse spleen, not in T cell areas. Antibody-targeted antigen delivery in vivo (hybrid anti-Langerin mAb containing OVA), T-cell division assay, immunolabeling of spleen sections Journal of immunology High 18322168
2011 Langerin captures measles virus on human primary Langerhans cells; immature LCs present MV antigens via HLA class II to CD4+ T cells but are not susceptible to productive MV infection and cannot cross-present exogenous MV to CD8+ T cells. Mature LCs can be infected by MV and present endogenously synthesized viral antigens to CD8+ T cells, but neither immature nor mature LCs cross-present MV. Primary human LC infection assays, anti-langerin antibody blocking, MHC class I/II antigen presentation assays with MV-specific T cells, UV-inactivated MV cross-presentation assay European journal of immunology High 21739428
2015 Langerin on primary human Langerhans cells routes internalized antigen to early endosomes (EEA1+), enhancing cross-presentation to CD8+ T cells; anti-langerin antibody-modified synthetic long peptides, but not anti-dectin-1, enhanced cross-presentation. Langerin-mediated internalization routes antigens to less proteolytic early endosomal compartments. Anti-langerin and anti-dectin-1 antibody-coupled SLP antigen delivery, early endosome co-localization (EEA1), CD8+ T-cell cross-presentation assay with primary human LCs Cellular & molecular immunology High 26456691
2015 Langerin recognizes hyaluronic acid on dendritic cells, mediating clustering (adhesion) between Langerhans cells and DCs; this LC-DC clustering leads to DC maturation and facilitates antigen transfer of HIV-1 to DCs for subsequent CD8+ T-cell activation. Hyaluronidase-2 upregulation by DC maturation degrades hyaluronic acid and abrogates LC-DC interactions. Anti-langerin antibody blocking, hyaluronic acid removal from DCs, LC-DC clustering assay, HIV-1 antigen transfer assay, CD8+ T-cell activation readout Journal of immunology Medium 26170391
2015 Langerin (CD207) serves as a phagocytic receptor for Yersinia pestis; Y. pestis invades Langerhans cells and langerin-transfected cells via interaction of core oligosaccharides with langerin. Shielding or truncating bacterial core oligosaccharides or adding purified langerin, anti-CD207 antibody, or competing oligosaccharides reduces invasion. Langerin-mediated uptake promotes Y. pestis dissemination to lymph nodes in a murine model. Y. pestis invasion assays with LCs and langerin transfectants, inhibitor competition assays (purified langerin, anti-CD207, oligosaccharides), murine in vivo infection model Immunology and cell biology Medium 25829141
2005 HPV 16 virus-like particles colocalize with langerin on the cell surface and in cytoplasmic vesicles of Langerhans cells by electron microscopy, and exhibit faster entry kinetics in LCs compared to DCs, entering near the nuclear membrane within 10 minutes; both LCs and DCs internalize HPV16 VLPs via a clathrin-dependent pathway into endosomal vesicles. Electron microscopy colocalization, time-course internalization experiments, clathrin inhibitor studies with HPV16 VLPs in primary LCs and DCs The Journal of general virology Medium 15831940

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 704 10661407
2007 Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nature medicine 462 17334373
2006 A major lung CD103 (alphaE)-beta7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins. Journal of immunology (Baltimore, Md. : 1950) 393 16455972
2008 Clearance of influenza virus from the lung depends on migratory langerin+CD11b- but not plasmacytoid dendritic cells. The Journal of experimental medicine 386 18591406
2007 Identification of a novel population of Langerin+ dendritic cells. The Journal of experimental medicine 385 18086865
2010 Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunological reviews 335 20193016
2007 Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state. The Journal of experimental medicine 325 18086862
2009 CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells. The Journal of experimental medicine 322 20038600
2007 The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells. The Journal of experimental medicine 307 18086861
2011 Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A. Proceedings of the National Academy of Sciences of the United States of America 228 21262813
2004 Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells. The Journal of clinical investigation 225 14991068
1999 The monoclonal antibody DCGM4 recognizes Langerin, a protein specific of Langerhans cells, and is rapidly internalized from the cell surface. European journal of immunology 211 10508244
2009 Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions. Proceedings of the National Academy of Sciences of the United States of America 184 19218433
2013 Langerin(neg) conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice. Proceedings of the National Academy of Sciences of the United States of America 155 23754427
2003 Characterization of carbohydrate recognition by langerin, a C-type lectin of Langerhans cells. Glycobiology 147 12626394
2003 Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin/CD207. The Journal of investigative dermatology 138 12542532
2008 Cutting edge: langerin/CD207 receptor on dendritic cells mediates efficient antigen presentation on MHC I and II products in vivo. Journal of immunology (Baltimore, Md. : 1950) 137 18322168
2002 Birbeck granules are subdomains of endosomal recycling compartment in human epidermal Langerhans cells, which form where Langerin accumulates. Molecular biology of the cell 133 11809842
2009 Antibody to Langerin/CD207 localizes large numbers of CD8alpha+ dendritic cells to the marginal zone of mouse spleen. Proceedings of the National Academy of Sciences of the United States of America 132 19168629
2002 Identification of mouse langerin/CD207 in Langerhans cells and some dendritic cells of lymphoid tissues. Journal of immunology (Baltimore, Md. : 1950) 129 11777972
2004 Functional comparison of the mouse DC-SIGN, SIGNR1, SIGNR3 and Langerin, C-type lectins. International immunology 124 15096474
2004 High and low affinity carbohydrate ligands revealed for murine SIGN-R1 by carbohydrate array and cell binding approaches, and differing specificities for SIGN-R3 and langerin. International immunology 117 15136555
2004 CD8 alpha- and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis. European journal of immunology 117 15162423
2008 Immunohistochemical expression of Langerin in Langerhans cell histiocytosis and non-Langerhans cell histiocytic disorders. The American journal of surgical pathology 108 18277880
2010 C-type lectin Langerin is a beta-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi. Molecular immunology 107 20097424
2014 Langerin-expressing dendritic cells in human tissues are related to CD1c+ dendritic cells and distinct from Langerhans cells and CD141high XCR1+ dendritic cells. Journal of leukocyte biology 103 25516751
2010 Structural basis for langerin recognition of diverse pathogen and mammalian glycans through a single binding site. Journal of molecular biology 101 21112338
2004 Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 99 15630529
2002 Identification and expression of mouse Langerin (CD207) in dendritic cells. International immunology 95 11978773
2005 Disruption of the langerin/CD207 gene abolishes Birbeck granules without a marked loss of Langerhans cell function. Molecular and cellular biology 86 15601833
2011 Comparative analysis reveals selective recognition of glycans by the dendritic cell receptors DC-SIGN and Langerin. Protein engineering, design & selection : PEDS 84 21540232
2008 Langerin expressing cells promote skin immune responses under defined conditions. Journal of immunology (Baltimore, Md. : 1950) 84 18354196
2005 Mouse lymphoid tissue contains distinct subsets of langerin/CD207 dendritic cells, only one of which represents epidermal-derived Langerhans cells. The Journal of investigative dermatology 77 16297200
2013 Langerin negative dendritic cells promote potent CD8+ T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays. Proceedings of the National Academy of Sciences of the United States of America 75 23386724
2009 Langerin+ CD8alpha+ dendritic cells are critical for cross-priming and IL-12 production in response to systemic antigens. Journal of immunology (Baltimore, Md. : 1950) 74 19923446
2011 Steady state migratory RelB+ langerin+ dermal dendritic cells mediate peripheral induction of antigen-specific CD4+ CD25+ Foxp3+ regulatory T cells. European journal of immunology 73 21469094
2011 Characterization of Langerin-expressing dendritic cell subsets in the normal cornea. Investigative ophthalmology & visual science 73 21482644
2014 Murine Langerin+ dermal dendritic cells prime CD8+ T cells while Langerhans cells induce cross-tolerance. EMBO molecular medicine 72 25085878
2011 Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross-presentation. European journal of immunology 72 21739428
2019 A Specific, Glycomimetic Langerin Ligand for Human Langerhans Cell Targeting. ACS central science 71 31139717
2009 Dual specificity of Langerin to sulfated and mannosylated glycans via a single C-type carbohydrate recognition domain. The Journal of biological chemistry 71 20026605
2011 Conditional deletion of TGF-βR1 using Langerin-Cre mice results in Langerhans cell deficiency and reduced contact hypersensitivity. Journal of immunology (Baltimore, Md. : 1950) 66 21998450
2010 Trimeric structure of langerin. The Journal of biological chemistry 65 20181944
2004 CD1a and langerin: acting as more than Langerhans cell markers. The Journal of clinical investigation 64 14991060
2015 Cross-presentation through langerin and DC-SIGN targeting requires different formulations of glycan-modified antigens. Journal of controlled release : official journal of the Controlled Release Society 60 25656175
2010 Langerin functions as an antiviral receptor on Langerhans cells. Immunology and cell biology 60 20309013
2019 Langerhans Cells Sense Staphylococcus aureus Wall Teichoic Acid through Langerin To Induce Inflammatory Responses. mBio 59 31088921
2009 Structural studies of langerin and Birbeck granule: a macromolecular organization model. Biochemistry 54 19175323
2007 The carbohydrate recognition domain of Langerin reveals high structural similarity with the one of DC-SIGN but an additional, calcium-independent sugar-binding site. Molecular immunology 54 18061677
2004 Ontogeny of Langerin/CD207 expression in the epidermis of mice. The Journal of investigative dermatology 50 15086552
2014 Inhibition of two temporal phases of HIV-1 transfer from primary Langerhans cells to T cells: the role of langerin. Journal of immunology (Baltimore, Md. : 1950) 49 25070850
2015 The C-type Lectin Langerin Functions as a Receptor for Attachment and Infectious Entry of Influenza A Virus. Journal of virology 45 26468543
2014 A population of Langerin-positive dendritic cells in murine Peyer's patches involved in sampling β-glucan microparticles. PloS one 45 24632738
2013 Common polymorphisms in human langerin change specificity for glycan ligands. The Journal of biological chemistry 45 24217250
2007 Production of monoclonal antibodies that recognize the extracellular domain of mouse langerin/CD207. Journal of immunological methods 45 17553520
2005 A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human Langerin gene. The Journal of investigative dermatology 43 15816828
2008 Expression of langerin/CD207 reveals dendritic cell heterogeneity between inbred mouse strains. Immunology 42 18217955
2013 Antigen-presenting cell candidates for HIV-1 transmission in human distal colonic mucosa defined by CD207 dendritic cells and CD209 macrophages. AIDS research and human retroviruses 41 24134315
2012 A Rab11A/myosin Vb/Rab11-FIP2 complex frames two late recycling steps of langerin from the ERC to the plasma membrane. Traffic (Copenhagen, Denmark) 40 22420646
2015 Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells. Cellular & molecular immunology 39 26456691
2009 Lack of retinoic acid leads to increased langerin-expressing dendritic cells in gut-associated lymphoid tissues. Gastroenterology 38 19914251
2007 Immunohistochemical analysis of langerin in langerhans cell histiocytosis and pulmonary inflammatory and infectious diseases. The American journal of surgical pathology 38 17527085
2004 Breast carcinoma cells promote the differentiation of CD34+ progenitors towards 2 different subpopulations of dendritic cells with CD1a(high)CD86(-)Langerin- and CD1a(+)CD86(+)Langerin+ phenotypes. International journal of cancer 38 15146561
2014 Caveolin-1 mediated uptake via langerin restricts HIV-1 infection in human Langerhans cells. Retrovirology 37 25551286
2012 Glycosaminoglycans are interactants of Langerin: comparison with gp120 highlights an unexpected calcium-independent binding mode. PloS one 36 23226363
2009 Langerin/CD207 positive dendritic-like cells in the haemopoietic tissues of salmonids. Fish & shellfish immunology 36 19630133
2016 Intradomain Allosteric Network Modulates Calcium Affinity of the C-Type Lectin Receptor Langerin. Journal of the American Chemical Society 35 27560542
2015 Host Langerin (CD207) is a receptor for Yersinia pestis phagocytosis and promotes dissemination. Immunology and cell biology 34 25829141
2015 Langerhans Cell-Dendritic Cell Cross-Talk via Langerin and Hyaluronic Acid Mediates Antigen Transfer and Cross-Presentation of HIV-1. Journal of immunology (Baltimore, Md. : 1950) 34 26170391
2013 Langerin+ dermal DC, but not Langerhans cells, are required for effective CD8-mediated immune responses after skin scarification with vaccinia virus. The Journal of investigative dermatology 34 24126845
2017 Ultraviolet B-Induced Maturation of CD11b-Type Langerin- Dendritic Cells Controls the Expansion of Foxp3+ Regulatory T Cells in the Skin. Journal of immunology (Baltimore, Md. : 1950) 33 29158419
2016 Bacterial Polysaccharide Specificity of the Pattern Recognition Receptor Langerin Is Highly Species-dependent. The Journal of biological chemistry 33 27903635
2016 (19)F NMR-Guided Design of Glycomimetic Langerin Ligands. ACS chemical biology 32 27458873
2004 Reproduction of Langerin/CD207 traffic and Birbeck granule formation in a human cell line model. The Journal of investigative dermatology 31 15191545
2021 Impact of Glycan Linkage to Staphylococcus aureus Wall Teichoic Acid on Langerin Recognition and Langerhans Cell Activation. ACS infectious diseases 30 33591717
2016 Red blood cells with elevated cytoplasmic Ca(2+) are primarily taken up by splenic marginal zone macrophages and CD207+ dendritic cells. Transfusion 30 27095001
2007 Rab11A controls the biogenesis of Birbeck granules by regulating Langerin recycling and stability. Molecular biology of the cell 30 17538027
2005 Human papillomavirus 16 virus-like particles use heparan sulfates to bind dendritic cells and colocalize with langerin in Langerhans cells. The Journal of general virology 30 15831940
2010 Langerin-expressing dendritic cells in gut-associated lymphoid tissues. Immunological reviews 29 20193022
2010 Langerin+ dermal dendritic cells are critical for CD8+ T cell activation and IgH γ-1 class switching in response to gene gun vaccines. Journal of immunology (Baltimore, Md. : 1950) 29 21187444
2009 Interleukin-17A is not expressed by CD207(+) cells in Langerhans cell histiocytosis lesions. Nature medicine 29 19424201
2007 Coexpression of CD1a, langerin and Birbeck's granules in Langerhans cell histiocytoses (LCH) in children: ultrastructural and immunocytochemical studies. Folia histochemica et cytobiologica 29 17378241
2006 Polymorphisms in human langerin affect stability and sugar binding activity. The Journal of biological chemistry 28 16567809
2020 CD1a+ and CD207+ cells are reduced in oral submucous fibrosis and oral squamous cell carcinoma. Medicina oral, patologia oral y cirugia bucal 27 31880289
2020 Depletion of langerin+ cells enhances cutaneous wound healing. Immunology 27 32307696
2011 Detection of intraepithelial and stromal Langerin and CCR5 positive cells in the human endometrium: potential targets for HIV infection. PloS one 27 21738639
2020 Circulating CD1c+ myeloid dendritic cells are potential precursors to LCH lesion CD1a+CD207+ cells. Blood advances 26 31899802
2016 CD1c-Related DCs that Express CD207/Langerin, but Are Distinguishable from Langerhans Cells, Are Consistently Present in Human Tonsils. Frontiers in immunology 26 27252701
2012 Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ T cell responses. Journal of immunology (Baltimore, Md. : 1950) 26 22291181
2019 Langerin+CD8+ Dendritic Cells in the Splenic Marginal Zone: Not So Marginal After All. Frontiers in immunology 25 31031751
2017 CD207+CD1a+ cells circulate in pediatric patients with active Langerhans cell histiocytosis. Blood 24 28847997
2003 TNF-alpha induces the generation of Langerin/(CD207)+ immature Langerhans-type dendritic cells from both CD14-CD1a and CD14+CD1a- precursors derived from CD34+ cord blood cells. European journal of immunology 24 12884872
2018 High affinity sugar ligands of C-type lectin receptor langerin. Biochimica et biophysica acta. General subjects 23 29631057
2016 Kinetic and Structural Studies of Interactions between Glycosaminoglycans and Langerin. Biochemistry 22 27447199
2011 Langerin, the "Catcher in the Rye": an important receptor for pathogens on Langerhans cells. European journal of immunology 22 21952811
2010 Directly transfected langerin+ dermal dendritic cells potentiate CD8+ T cell responses following intradermal plasmid DNA immunization. Journal of immunology (Baltimore, Md. : 1950) 21 20713888
2010 Langerin+ dendritic cells are responsible for LPS-induced reactivation of allergen-specific Th2 responses in postasthmatic mice. Mucosal immunology 21 21048704
2020 Rational Design of a DNA-Scaffolded High-Affinity Binder for Langerin. Angewandte Chemie (International ed. in English) 20 32749019
2018 Toll-like receptor 4 attenuates a murine model of atopic dermatitis through inhibition of langerin-positive DCs migration. Experimental dermatology 20 29851146
2014 A protective role of murine langerin⁺ cells in immune responses to cutaneous vaccination with microneedle patches. Scientific reports 20 25130187

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