A proposed of model for mannose receptor–mediated endocytosis of ADAMTS13 in dendritic cells. The mannose receptor (MR) consists of an N-terminal cysteine-rich domain (CR) and 8 C-type lectin-like carbohydrate recognition domains (CTLDs 1-8) that bind glycoproteins terminated by D-mannose, L-fucose, or N-acetylglucosamine. The 4 to 7 CTLDs are shown to bind ADAMTS13. Once the MR-ADAMTS13 complex is internalized, it is transported to the endosomal pathway including early endosome (EE), late endosome (LE), and lysosome (LS). In the early endosome, the endocytosed ADAMTS13 may be dissociated from the MR and loaded on the MHC class I molecules (MHC I) for activation of the CD8⁺ T cells, termed cross-presentation. Other studies have demonstrated that certain soluble protein antigens taken up through the MR pathway can be targeted to the LE and LS for proteolytic degradation. The antigen-derived peptides can then be loaded on the MHC II molecules for presentation to the CD4⁺ T cells. The endocytosed ADAMTS13 is primarily detected in the early endosome of iDCs, suggesting that other pathways for endocytosis of ADAMTS13 may also be necessary for presenting the antigenic peptides to the CD4⁺ cells. It may be possible that on induction of iDC maturation, the antigen can be transported to the MHC II molecules for presentation to the CD4⁺ cells.