Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice

Cathepsins have been implicated in the degradation of proteins destined for the MHC class II processing pathway and in the proteolytic removal of inva riant chain (Ii), a critical regulator of MHC class II function. Mice lacki ng the lysosomal cysteine proteinase cathepsin S (catS) demonstrated a prof ound inhibition of Ii degradation in professional APC in vivo. A marked var iation in the generation of MHC class II-bound Ii fragments and presentatio n of exogenous proteins was observed between B cells, dendritic cells, and macrophages lacking catS. CatS-deficient mice showed diminished susceptibil ity to collagen-induced arthritis, suggesting a potential therapeutic targe t for regulation of immune responsiveness.