Possible mechanisms to explain how exogenous peptides could be processed to form MHC class I–binding peptides, some of which may constitute cryptic epitopes. Peptides derived from a vaccine (step 1) could be cleaved by serum proteases (SP) (step 2) or cell surface proteases (CSP) on the APC (step 3) to form products capable of binding to cell surface MHC class I molecules that are temporarily empty. Alternatively, the exogenously added peptide representing the minimal CTL epitope may bind to surface MHCmolecules by displacing endogenously-bound peptides (step 4). Endocytosed peptides (step 5) may be cleaved by resident proteases (P) in endosomal compartments (EC) or may gain access to the cytoplasm (step 7) where proteasomes (PS) may cleave them. The cytoplasmic peptides gain access to the endoplasmic reticulum (ER) through the action of the transporter associated with antigen processing (TAP) (step 8). Once in the ER, peptides may be additionally trimmed by resident aminopeptidases (AP), where they bind to empty MHC class I molecules (step 9). The peptide/MHC complexes travel via the Golgi apparatus (step 10) to the cell surface, where they are exposed to T cell interactions (step 11). Peptides that are endocytosed can also bind to MHC class I molecules that recycle through ECs (step 13) to the cell surface (step 14).