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

doi:10.1038/80852

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 journal › Article › peer-review

221 Scopus citations

Abstract

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 language	English
Pages (from-to)	413-418
Number of pages	6
Journal	Nature Immunology
Volume	1
Issue number	5
DOIs	https://doi.org/10.1038/80852
State	Published - 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.).

Funding

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.).

Funders	Funder number
CTL Immunotherapies Corporation
NIH/NIDA	DA 02243
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse	R01DA002243
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse
Merck KGaA
European Commission	95-0263
European Commission
Deutsche Forschungsgemeinschaft	Ra369/4-1
Deutsche Forschungsgemeinschaft

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/80852

Cite this

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title = "Two new proteases in the MHC class I processing pathway",

abstract = "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.",

author = "Lars Stoltze and Markus Schirle and Gerold Schwarz and Christian Schr{\"o}ter and Thompson, \{Michael W.\} and Hersh, \{Louis B.\} and Hubert Kalbacher and Stefan Stevanovic and Rammensee, \{Hans Georg\} and Hansj{\"o}rg Schild",

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.).",

year = "2000",

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doi = "10.1038/80852",

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AU - Stoltze, Lars

AU - Schirle, Markus

AU - Schwarz, Gerold

AU - Schröter, Christian

AU - Thompson, Michael W.

AU - Hersh, Louis B.

AU - Kalbacher, Hubert

AU - Stevanovic, Stefan

AU - Rammensee, Hans Georg

AU - Schild, Hansjörg

N1 - 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.).

PY - 2000/11

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AB - 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.

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ER -

Two new proteases in the MHC class I processing pathway

Abstract

Bibliographical note

Funding

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