Creation versus destruction of T cell epitopes in the class II MHC pathway

Proteases perform two key roles in the class II MHC antigen processing pathway. They initiate removal of the invariant chain chaperone for class II MHC and they generate peptides from foreign and self proteins for eventual capture and display to T cells. How a balance is achieved between generation of suitable peptides versus their complete destruction in an aggressive proteolytic environment is not known. Nor is it known in most cases which proteases are actually involved in antigen processing. Our recent studies have identified asparagine endopeptidase (AEP or legumain) as an enzyme that contributes to both productive and destructive antigen processing in the class II MHC pathway. The emerging consensus seems to be that individual proteolytic enzymes make clear and non-redundant contributions to antigen processing.