PathwayStep6603 PathwayStep6602 PathwayStep6601 PathwayStep6600 Translocation of peptide bound MHC class I complex to cell surface Loading of antigen peptide onto MHC class I molecule Trimming of peptides by IRAP in endocytic vesicles Antigen processing by cathepsin S in endosoytic vesicle Endosomal/Vacuolar pathway Authored: Garapati, P V, 2011-03-28 Edited: Garapati, P V, 2011-03-28 GENE ONTOLOGYGO:0002480 Pubmed15308097 Pubmed18376401 Reactome Database ID Release 431236977 Reactome, http://www.reactome.org ReactomeREACT_111168 Reviewed: Desjardins, M, English, L, 2011-05-13 Some antigens are cross-presented through a vacuolar mechanism that involves generation of antigenic peptides and their loading on to MHC-I molecules within the endosomal compartment in a proteasome and TAP-independent manner. Antigens within the endosome are processed by cathepsin S and other proteases into antigenic peptides. Loading of these peptides onto MHC-I molecules occurs directly within early and late endosomal compartments. Why certain antigens are cross-presented exclusively by the cytosolic pathway while others use the vacuolar pathway is unknown. It may be because some epitopes cannot be generated by endosomal proteolysis, or are completely destroyed. Alternatively, the physical form of the antigen may influence its accessibility to the endosomal or vacuolar pathways (Shen et al. 2004).