Human DC cross-presentation of cell-associated antigens. Dead cells are internalized by DCs via mechanisms dependent on cytoskeletal actin rearrangements or functional ion channels, which are required for phagocytosis and macropinocytosis. After entering the cell, the antigens are enclosed in the cell's endosomal compartment and shipped from neutral to subsequently more acidic endosomal vesicles. In a late acid endosomal compartment the antigens undergo proteolysis; this involves the aspartic protease cathepsin D, which appears to be essential for cross-presentation of MP. Cathepsin D may be required for degradation of the antigens or antigen complexes into sizes/forms that can be transported out to the cytosol. When the antigen has entered the cytosol it is processed by the proteasome. The proteasome products are transported via TAP into the lumen of ER where the peptides are loaded on newly synthesized MHC class I molecules and subsequently transported out to the DC surface for presentation.