Mannose-recognizing C-type lectin receptors (CLRs)

Mannose-recognizing C-type lectin receptors (CLRs), such as DC-SIGN (CD209) and the Mannose Receptor (CD206), are essential pattern recognition receptors primarily expressed on dendritic cells and macrophages [UniProt Q9NNX6; UniProt P22897]. They play a critical role in the innate immune system by identifying high-mannose carbohydrate motifs on the surface of various pathogens, including viruses like HIV-1 and bacteria like Mycobacterium tuberculosis [Nature Reviews Immunology, 2009]. Upon binding, these receptors facilitate the internalization of pathogens or mannosylated drugs through endocytosis, leading to antigen processing and the activation of adaptive immune responses [Expert Opinion on Biological Therapy, 2004]. In drug development, these receptors are targeted to improve vaccine delivery to professional antigen-presenting cells or for diagnostic imaging of the lymphatic system using agents like Technetium (99mTc) tilmanocept [FDA, 2013]. However, their function can be subverted by certain pathogens to evade immune detection or facilitate cellular entry, making them complex but valuable therapeutic targets [Nature Reviews Immunology, 2009].

Other names

DC-SIGNCD209Mannose receptorCD206MRC1Dectin-2LangerinCD207Mannose-binding C-type lectin receptorsDendritic cell C-type lectin receptors recognizing mannose

These receptors recognize and bind mannose-containing glycans on the surface of pathogens or therapeutic agents via their carbohydrate-recognition domains (CRDs) [Nature Reviews Immunology, 2009]. This binding initiates receptor-mediated endocytosis, which transports the ligand into the endo-lysosomal pathway for processing and subsequent presentation of antigens on MHC molecules to T cells [Expert Opinion on Biological Therapy, 2004]. In diagnostic applications, ligands like tilmanocept bind to the Mannose Receptor (CD206) to facilitate the visualization of receptor-expressing macrophages in lymph nodes [FDA, 2013].