Human epidermal Langerhans cells lack functional mannose receptors and a fully developed endosomal/lysosomal compartment for loading of HLA class II molecules

Langerhans cells (LC) represent the dendritic cell (DC) lineage in the epid ermis. They capture and process antigens in the skin and subsequently migra te to the draining lymph nodes to activate naive T cells. Efficient uptake and processing of protein antigens by LC would, therefore, seem a prerequis ite. We have now compared the capacity of human epidermal LC, blood-derived DC and peripheral blood mononuclear cells to endocytose and present (manno sylated) antigens to antigen-specific T cells. Moreover, we have determined the expression of mannose receptors, and the composition of the intracellu lar endosomal/lysosomal MHC class Ii-positive compartment. The results indi cate that LC have poor endocytic capacity and do not exploit mannose recept or-mediated endocytosis pathways. Furthermore, the composition of the class II compartment in LC is distinct from that in other antigen-presenting cel ls and is characterized by the presence of relatively tow levels of lysosom al markers. These results underscore the unique properties of LC and indica te that LC are relatively inefficient in antigen uptake, processing and pre sentation. This may serve to avoid hyper-responsiveness to harmless protein antigens that are likely to be frequently encountered in the skin due to ( mechanical) skin damage.