| Langerin (CD207) is a type II transmembrane C‑type lectin receptor selectively expressed by Langerhans cells and defined subsets of dendritic cells, where it functions as a sugar-binding endocytic receptor that links pathogen recognition at epithelial barriers to antigen processing and T‑cell activation. The protein comprises a short cytoplasmic tail, a single transmembrane segment, a coiled-coil neck that mediates homotrimer formation, and a luminal C‑type lectin carbohydrate recognition domain that binds mannose-, fucose-, and N‑acetylglucosamine-containing glycans and β‑glucans on the surfaces of viruses, fungi, and bacteria, and trimerization increases avidity and specificity for multivalent glycan ligands. Langerin localizes to the plasma membrane and to Birbeck granules, which are rod- or racket-shaped organelles formed by superimposed and zippered membranes whose biogenesis depends on Langerin expression and whose ultrastructure reflects Langerin-driven membrane rearrangements; mutational analysis shows that defined regions of Langerin are required for Birbeck granule formation, identifying this receptor as a key organizer of these LC-specific organelles. Ligand engagement induces rapid clathrin-independent internalization of Langerin–cargo complexes from the cell surface into Birbeck granules and associated endosomal structures, where captured antigens are processed and loaded onto MHC class II and, via cross-presentation, onto MHC class I molecules, and in vivo targeting of antigen to Langerin on dendritic cells results in efficient activation and proliferation of both CD4⁺ and CD8⁺ T cells with durable peptide–MHC display. This internalization and routing pathway allows Langerin to act as an antiviral and antifungal barrier at mucosal and cutaneous surfaces; HIV‑1, measles virus, and mycobacterial and fungal glycoconjugates are bound by Langerin and directed into Birbeck granules, where virions and microbial components are degraded and processed for antigen presentation rather than productively infecting Langerhans cells, thereby limiting pathogen transmission under conditions where Langerin expression and function are intact. Langerin is regulated by cytokines and tissue context, with TGF‑β1 and local epithelial factors promoting its expression during LC differentiation, and its expression is generally downregulated as Langerhans cells undergo terminal maturation and migration to lymph nodes, making CD207 a reliable marker of Langerhans cell identity and differentiation state in skin and mucosal epithelia as well as in specialized dendritic subsets in lymphoid and pulmonary tissues. Genetic variation in CD207 that reduces Langerin function or alters glycan binding compromises mannose recognition and is associated with increased susceptibility to cutaneous infection and changes in LC-mediated barrier immunity, and langerin expression is exploited diagnostically to distinguish Langerhans cell histiocytosis from non‑Langerhans histiocytic proliferations and to map Langerhans cell–rich inflammatory lesions in oral, skin, and pulmonary disease. |
