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Why the Structure but Not the Activity of the Immunoproteasome Subunit Low Molecular Mass Polypeptide 2 Rescues Antigen Presentation

Why the Structure but Not the Activity of the Immunoproteasome Subunit Low Molecular Mass Polypeptide 2 Rescues Antigen Presentation

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BASLER, Michael, Christoph LAUER, Jacqueline MOEBIUS, Reinhold WEBER, Michael PRZYBYLSKI, Alexei F. KISSELEV, Christopher TSU, Marcus GRÖTTRUP, 2012. Why the Structure but Not the Activity of the Immunoproteasome Subunit Low Molecular Mass Polypeptide 2 Rescues Antigen Presentation. In: The Journal of Immunology. 189(4), pp. 1868-1877. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/jimmunol.1103592

@article{Basler2012Struc-21997, title={Why the Structure but Not the Activity of the Immunoproteasome Subunit Low Molecular Mass Polypeptide 2 Rescues Antigen Presentation}, year={2012}, doi={10.4049/jimmunol.1103592}, number={4}, volume={189}, issn={0022-1767}, journal={The Journal of Immunology}, pages={1868--1877}, author={Basler, Michael and Lauer, Christoph and Moebius, Jacqueline and Weber, Reinhold and Przybylski, Michael and Kisselev, Alexei F. and Tsu, Christopher and Gröttrup, Marcus} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/21997"> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-02-20T13:48:50Z</dc:date> <dcterms:abstract xml:lang="eng">The proteasome is responsible for the generation of most epitopes presented on MHC class I molecules. Treatment of cells with IFN-gamma leads to the replacement of the constitutive catalytic subunits beta1, beta2, and beta5 by the inducible subunits low molecular mass polypeptide (LMP) 2 (beta1i), multicatalytic endopeptidase complex-like-1 (beta2i), and LMP7 (beta5i), respectively. The incorporation of these subunits is required for the production of numerous MHC class I-restricted T cell epitopes. The structural features rather than the proteolytic activity of an immunoproteasome subunit are needed for the generation of some epitopes, but the underlying mechanisms have remained elusive. Experiments with LMP2-deficient splenocytes revealed that the generation of the male HY-derived CTL-epitope UTY(246-254) was dependent on LMP2. Treatment of male splenocytes with an LMP2-selective inhibitor did not reduce UTY(246-254) presentation, whereas silencing of beta1 activity increased presentation of UTY(246-254). In vitro degradation experiments showed that the caspase-like activity of beta1 was responsible for the destruction of this CTL epitope, whereas it was preserved when LMP2 replaced beta1. Moreover, inhibition of the beta5 subunit rescued the presentation of the influenza matrix 58-66 epitope, thus suggesting that a similar mechanism can apply to the exchange of beta5 by LMP7. Taken together, our data provide a rationale why the structural property of an immunoproteasome subunit rather than its activity is required for the generation of a CTL epitope.</dcterms:abstract> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:contributor>Kisselev, Alexei F.</dc:contributor> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Gröttrup, Marcus</dc:contributor> <dc:creator>Weber, Reinhold</dc:creator> <dc:creator>Tsu, Christopher</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-02-20T13:48:50Z</dcterms:available> <dc:contributor>Przybylski, Michael</dc:contributor> <dcterms:bibliographicCitation>The Journal of Immunology ; 189 (2012), 4. - S. 1868-1877</dcterms:bibliographicCitation> <dc:contributor>Moebius, Jacqueline</dc:contributor> <dc:creator>Gröttrup, Marcus</dc:creator> <dc:creator>Kisselev, Alexei F.</dc:creator> <dc:rights>deposit-license</dc:rights> <dc:contributor>Tsu, Christopher</dc:contributor> <dcterms:issued>2012</dcterms:issued> <dc:creator>Basler, Michael</dc:creator> <dc:creator>Lauer, Christoph</dc:creator> <dc:contributor>Basler, Michael</dc:contributor> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/21997"/> <dc:creator>Moebius, Jacqueline</dc:creator> <dcterms:title>Why the Structure but Not the Activity of the Immunoproteasome Subunit Low Molecular Mass Polypeptide 2 Rescues Antigen Presentation</dcterms:title> <dc:contributor>Lauer, Christoph</dc:contributor> <dc:contributor>Weber, Reinhold</dc:contributor> <dc:language>eng</dc:language> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dc:creator>Przybylski, Michael</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103605204-4002607-1"/> </rdf:Description> </rdf:RDF>

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