The proteasome generates exact major histocompatibility complex (MHC) class
I ligands as well as NH2-terminal-extended precursor peptides, The proteas
es responsible for the final NH2-terminal trimming of the precursor peptide
s had, until now, not been determined, By using specific selective criteria
we purified two cytosolic proteolytic activities, puromycin-sensitive amin
opeptidase and bleomycin hydrolase,These proteases could remove NH2-termina
l 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.