Langerin/CD207 sheds light on formation of birbeck granules and their possible function in Langerhans cells.

Langerhans cells (LCs) are immature dendritic cells of epidermis and epithelia, playing a sentinel role through their specialized function in antigen capture, and their capacity to migrate to secondary lymphoid tissue to initiate specific immunity. A unique feature of LCs is the presence of Birbeck granules (BGs), which are disks of two limiting membranes, separated by leaflets with periodic "zipperlike" striations. The recent identification of Langerin/CD207 has allowed researchers to decipher the mechanism of BG formation and approach an understanding of their function. Langerin is a type II lectin with mannose specificity expressed by LCs in epidermis and epithelia. Remarkably, transfection of Langerin cDNA into fibroblasts creates a dense network of membrane structures with features typical of BGs. Furthermore, mutated and deleted forms of Langerin have been engineered to map the functional domains essential for BG formation. Langerin is a potent LC-specific regulator of membrane superimposition and zippering, representing a key molecule to trace LCs and to probe BG function.