Freshly isolated epidermal Langerhans cells (LC) can actively process native protein antigens, but are weak in sensitizing helper T cells. During culture, when LC mature into potent immunostimulatory dendritic cells, T cell sensitizing capacity develops but antigen processing capacity is downregulated. Processing of exogenous antigens for class II-restricted antigen presentation involves acidic organelles. We used the DAMP-technique to monitor acidic organelles at the ultrastructural level in fresh, as well as cultured, mouse and human LC. We observed that the loss of antigen processing capacity with culture of LC was reflected by the disappearance of certain acidic organelles, namely endosomes (particularly early ones), and the hitherto enigmatic LC granules ("Birbeck Granules"). Our findings support the notion that endosomes are critical for antigen processing and suggest that LC granules might be involved as well.

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