The role of lysosomal proteinases in MHC class II-mediated antigen processing and presentation

The recent analysis of cathepsin-deficient mice has shed light upon the rol e of lysosomal proteinases in the MHC class II processing and presentation pathway. Ubiquitous expression and involvement in the terminal degradation of proteins that intersect the endocytic pathway were previously perceived to be the hallmarks of these proteinases. However, recent evidence has demo nstrated that several cathepsins are expressed in a tissue-specific fashion and that partial proteolysis of specific biological targets is a key funct ion of cathepsins in antigen processing. Our work has focused on the differ ential expression of the cysteine proteinases cathepsins L (CL) and S (CS) and its pertinence to the generation of MHC class II: peptide complexes. An alysis of CL-deficient mice revealed a profound defect in invariant chain d egradation in thymic cortical epithelial cells but not in bone marrow-deriv ed antigen-presenting cells (APCs) (B cells, dendritic cells, and macrophag es). The tissue-specific deficiency reflected the restricted pattern of exp ression of CL and CS in these cell types - CL is expressed in thymic cortic al epithelial cells but not in DC or B cells, while CS exhibits the opposit e expression pattern. The differential expression of proteinases by distinc t APCs may affect the types of peptides that are presented to T cells and t hereby the immune responses that are ultimately generated.