CD1a and langerin: acting as more than Langerhans cell markers

Langerhans cells (LCs) represent a unique DC subset populating the outermost body surface, i.e., the epidermis.Although CD1a and langerin (CD207) are used as specific markers to distinguish LCs from other DC subsets, their immunological functions have remained mostly unknown.A new paper (see the related article beginning on page 701) demonstrates that LCs utilize these markers to induce cellular immune responses to Mycobacterium leprae: CD1a mediates the presentation of nonpeptide antigens to T cells, while langerin facilitates uptake of microbial fragments and perhaps their delivery to a specialized subcellular compartment. Langerhans cell markersAs a tissue constantly exposed to external insults, the skin is equipped with layers of protective mechanisms.Stratum corneum serves as a physical barrier against infectious microbes, foreign proteins, and harmful chemicals, and keratinocytes produce a wide array of pro-and anti-inflammatory cytokines, as well as antimicrobial peptides.As a skin resident member of the DC family of APCs, Langerhans cells (LCs) initiate both innate and adaptive immune responses to skin-relevant antigens, thereby acting as immunological sentinels.Although LCs were discovered in 1868 by gold chloride staining as a highly dendritic epidermal cell population, their lineage or function remained unknown until the 1960s and 1970s when appropriate LC "markers" were discovered.These include surface I-A molecules (i.e., murine MHC class II molecules; refs. 1 and 2), membrane-associated enzymatic activities to hydrolyze extracellular ATP (ecto-ATPase) (3), and rod/tennis racket-shaped intracellular organelles (Birbeck granules) (4).More specific markers, such as CD1a ( 5), E-cadherin (6), and langerin (7), are now known to distinguish LCs from other DC subsets.Although identified initially as LC markers, these molecules have subsequently been shown to play functional roles in various