CD1c molecules broadly survey the endocytic system

The ability of antigen-presenting cells to sample distinct intracellular co mpartments is crucial for microbe detection. Major histocompatibility compl ex class I and class II molecules sample the cytosol or the late endocytic compartment, allowing detection of microbial peptide antigens that arise in distinct intracellular compartments. In contrast. CD1a and CD1b molecules mediate the presentation of lipid and glycolipid antigens and differentiall y sample early recycling endosomes or late endocytic compartments. respecti vely, that contain distinct sets of lipid antigens. Here. we show that, unl ike the other CD1 isoforms or major histocompatibility complex molecules th at each sample restricted only intracellular compartments. CD1c is remarkab le in that it distributes broadly throughout the endocytic system and is ex pressed in both recycling endosomes and late endocytic compartments. Furthe r, in contrast to CD1b, which requires an acidic environment to function, a ntigen presentation by CD1c was able to overcome dependence on vesicular ac idification. Because CD1c is expressed on essential antigen-presenting cell s, such as epidermal Langerhans cells (in the absence of CD1b), or on B cel ls (without cola or -b). we suggest that CD1c molecules allow a comprehensi ve survey for lipid antigens throughout the endocytic system even in the ab sence of other CD1 isoforms.