Two new proteases in the MHC class I processing pathway

The proteasome generates exact major histocompatibility complex (MHC) class I ligands as well as NH2-terminal-extended precursor peptides, The proteases responsible for the final NH2-terminal trimming of the precursor peptides had, until now, not been determined, By using specific selective criteria we purified two cytosolic proteolytic activities, puromycin-sensitive aminopeptidase and bleomycin hydrolase,These proteases could remove NH2-terminal amino acids from the vesicular stomatitis virus nucleoprotein cytotoxic T cell epitope 52-59 (RGYVYQGL) resulting, in combination with proteasomes, in the generation of the correct epitope, Our data provide evidence for the existence of redundant systems acting downstream of the proteasome in the antigen-processing pathway for MHC class I molecules.