Two new proteases in the MHC class I processing pathway

Lars Stoltze, Markus Schirle, Gerold Schwarz, Christian Schröter, Michael W. Thompson, Louis B. Hersh, Hubert Kalbacher, Stefan Stevanovic, Hans Georg Rammensee, Hansjörg Schild

Research output: Contribution to journalArticlepeer-review

215 Scopus citations


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.

Original languageEnglish
Pages (from-to)413-418
Number of pages6
JournalNature Immunology
Issue number5
StatePublished - Nov 2000

Bibliographical note

Funding Information:
Acknowledgements We thank L.Yakes for reading the manuscript. Supported by the Deutsche Forschungsgemeinschaft (Leibnizprogram Ra369/4-1, to H. G. R.); Sonderforschungsbereich 510 (to H. S.); the European Union (Biomed 95-0263), Merck KGaA (Darmstadt, Germany), CTL Immunotherapies Corporation (Chatsworth, CA, USA) and a grant from the NIH/NIDA, DA 02243 (to L. B. H.).

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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