Ty. Nakagawa et Ay. Rudensky, The role of lysosomal proteinases in MHC class II-mediated antigen processing and presentation, IMMUNOL REV, 172, 1999, pp. 121-129
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.