CATHEPSIN-B AND CATHEPSIN-D ARE DISPENSABLE FOR MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-MEDIATED ANTIGEN PRESENTATION

Antigen presentation by major histocompatibility complex (MHC) class I I molecules requires the participation of different proteases in the e ndocytic route to degrade endocytosed antigens as well as the MHC clas s II-associated invariant chain (Ii). Thus far, only the cysteine prot ease cathepsin (Cat) S appears essential for complete destruction of I i. The enzymes involved in degradation of the antigens themselves rema in to be identified. Degradation of antigens in vitro and experiments using protease inhibitors have suggested that Cat B and Cat D, two maj or aspartyl and cysteine proteases, respectively, are involved in anti gen degradation. We have analyzed the antigen-presenting properties of cells derived from mice deficient in either Cat B or Cat D. Although the absence of these proteases provoked a modest shift in the efficien cy of presentation of some antigenic determinants, the overall capacit y of Cat B-/- or Cat D-/- antigen-presenting cells was unaffected. Deg radation of Ii proceeded normally in Cat B-/- splenocytes, as it did i n Cat D-/- cells. We conclude that neither Cat B nor Cat D are essenti al for MHC class II-mediated antigen presentation.