Two new proteases in the MHC class I processing pathway

• Published in: Nature immunology Vol. 1; no. 5; pp. 413 - 418
• Main Authors: Schild, Hansjörg, Stoltze, Lars, Schirle, Markus, Schwarz, Gerold, Schröter, Christian, Thompson, Michael W, Hersh, Louis B, Kalbacher, Hubert, Stevanovic, Stefan, Rammensee, Hans-Georg
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.11.2000
• Subjects: Amino Acid Chloromethyl Ketones - pharmacology; Amino Acid Sequence; Amino acids; Aminopeptidase; Aminopeptidases - isolation & purification; Aminopeptidases - metabolism; Animals; Antigen processing; Antigens, Viral - chemistry; Antigens, Viral - genetics; Antigens, Viral - metabolism; Bleomycin; Cell Line; Cysteine Endopeptidases - isolation & purification; Cysteine Endopeptidases - metabolism; Cytotoxicity; Endopeptidases - isolation & purification; Endopeptidases - metabolism; Epitopes; Epitopes - chemistry; Epitopes - genetics; Epitopes - metabolism; Histocompatibility Antigens Class I - metabolism; Humans; Hydrolase; Ligands; Lymphocytes T; Major histocompatibility complex; Mice; Molecular Sequence Data; Multienzyme Complexes - metabolism; Nucleocapsid - genetics; Nucleocapsid - immunology; Nucleocapsid - metabolism; Nucleocapsid Proteins; Peptides; Proteasome Endopeptidase Complex; Proteasomes; Protein Processing, Post-Translational - drug effects; Proteolysis; Puromycin; Stomatitis; Vesicular stomatitis Indiana virus - genetics; Vesicular stomatitis Indiana virus - immunology
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/80852

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.