Endocytic compartments contain many cysteine proteases such as cathepsin S that can generate cross-presented peptides. Cathepsins may participate in the generation of MHC class II-presentated peptides (Villadangos et al. 1999). Shen et al. (2004) demonstrated that cathepsin S contributes to TAP-independent cross-presentation in vivo, showing that ovalbumin was cross-presented by denritic cells (DCs) through both TAP-dependent and TAP-independent pathways. The TAP-independent pathway was sensitive to the cystine protease inhibitor leupeptin, but not to proteasome inhibitors. Further experiments with knockout mice showed that cathepsin S contributed to cross-presentation. DCs lacking cathepsin S lack the TAP-independent pathway (Khor et al. 2008, Shen et al. 2004).