{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:20:54Z","timestamp":1779344454439,"version":"3.51.4"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2000,7,1]],"date-time":"2000-07-01T00:00:00Z","timestamp":962409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The proteasome is a large protease complex that generates most of the peptide ligands of MHC class I molecules either in their final form or in the form of N-terminally extended precursors. Upon the stimulation of cells with IFN-\u03b3, three constitutively expressed subunits of the 20S proteasome are replaced by the inducible subunits LMP2 (low-molecular mass polypeptide 2), LMP7, and MECL-1 (multicatalytic endopeptidase complex-like-1) to form so-called immunoproteasomes. We show in this study that overexpression of these three subunits in triple transfectants led to a marked enhancement in the H-2Ld-restricted presentation of the immunodominant nonameric epitope NP118, which is derived from the nucleoprotein (NP) of lymphocytic choriomeningitis virus. Overexpression of the \u03b1 and \u03b2 subunits of the IFN-\u03b3-inducible proteasome regulator PA28, in contrast, did not have a comparable effect. In vitro, immunoproteasomes as compared with constitutive proteasomes generated higher amounts of 11- and 12-mer fragments containing the NP118 epitope. These are likely to be cytosolic precursors of NP118, as a proline anchor residue in the second position of NP118 may interfere with TAP-mediated transport of the nonameric epitope itself. In conclusion, we provide evidence that up-regulation of the three inducible subunits, LMP2, LMP7, and MECL-1, can result in a marked improvement of Ag presentation and that, depending on the epitope, PA28 and immunoproteasomes may differentially affect Ag processing.<\/jats:p>","DOI":"10.4049\/jimmunol.165.2.768","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T03:02:33Z","timestamp":1398135753000},"page":"768-778","source":"Crossref","is-referenced-by-count":95,"title":["Overexpression of the Proteasome Subunits LMP2, LMP7, and MECL-1, But Not PA28\u03b1\/\u03b2, Enhances the Presentation of an Immunodominant Lymphocytic Choriomeningitis Virus T Cell Epitope"],"prefix":"10.1093","volume":"165","author":[{"given":"Katrin","family":"Schwarz","sequence":"first","affiliation":[{"name":"Research Department, Cantonal Hospital St. Gall , St. Gallen ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maries","family":"van den Broek","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, Department of Pathology, University Hospital Zu\u0308rich , Zu\u0308rich ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Kostka","sequence":"additional","affiliation":[{"name":"Max-Delbru\u0308ck Center for Molecular Medicine , Berlin-Buch ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regine","family":"Kraft","sequence":"additional","affiliation":[{"name":"Max-Delbru\u0308ck Center for Molecular Medicine , Berlin-Buch ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Soza","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry, Medical Faculty (Charite\u0301), Humboldt University , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunter","family":"Schmidtke","sequence":"additional","affiliation":[{"name":"Research Department, Cantonal Hospital St. Gall , St. Gallen ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter-M","family":"Kloetzel","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry, Medical Faculty (Charite\u0301), Humboldt University , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Groettrup","sequence":"additional","affiliation":[{"name":"Research Department, Cantonal Hospital St. Gall , St. Gallen ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,7,15]]},"reference":[{"key":"2025032907470920100_R1","first-page":"213","volume-title":"Annu. 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Biol.","year":"1995"},{"key":"2025032907470920100_R22","first-page":"1","volume-title":"J. Exp. Med.","year":"1996"},{"key":"2025032907470920100_R23","first-page":"863","volume-title":"Eur. J. Immunol.","year":"1996"},{"key":"2025032907470920100_R24","first-page":"2361","volume-title":"J. Immunol.","year":"1996"},{"key":"2025032907470920100_R25","first-page":"8970","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2025032907470920100_R26","first-page":"97","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032907470920100_R27","first-page":"37","volume-title":"FEBS Lett.","year":"1995"},{"key":"2025032907470920100_R28","first-page":"7","volume-title":"J. Mol. Biol.","year":"1994"},{"key":"2025032907470920100_R29","first-page":"639","volume-title":"Nature","year":"1997"},{"key":"2025032907470920100_R30","first-page":"5651","volume-title":"Biochemistry","year":"1999"},{"key":"2025032907470920100_R31","first-page":"27994","volume-title":"J. Biol. 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Methods","year":"1991"},{"key":"2025032907470920100_R42","first-page":"247","volume-title":"Virology","year":"1983"},{"key":"2025032907470920100_R43","first-page":"943","volume-title":"EMBO J.","year":"1986"},{"key":"2025032907470920100_R44","first-page":"369","volume-title":"lacZ inducible, antigen\/MHC-specific T cell hybrids. Int. Immunol.","year":"1994"},{"key":"2025032907470920100_R45","first-page":"1481","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2025032907470920100_R46","first-page":"6715","volume-title":"J. Immunol.","year":"1998"},{"key":"2025032907470920100_R47","first-page":"349","volume-title":"Virology","year":"1997"},{"key":"2025032907470920100_R48","first-page":"554","volume-title":"Eur. J. Immunol.","year":"1995"},{"key":"2025032907470920100_R49","first-page":"1641","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032907470920100_R50","first-page":"23062","volume-title":"J. Biol. Chem.","year":"1998"},{"key":"2025032907470920100_R51","first-page":"307","volume-title":"Chem. Biol.","year":"1998"},{"key":"2025032907470920100_R52","first-page":"13946","volume-title":"Biochemistry","year":"1997"},{"key":"2025032907470920100_R53","first-page":"12504","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2025032907470920100_R54","first-page":"463","volume-title":"Nature","year":"1997"},{"key":"2025032907470920100_R55","first-page":"25200","volume-title":"J. Biol. Chem.","year":"1997"},{"key":"2025032907470920100_R56","first-page":"11","volume-title":"FEBS Lett.","year":"1999"},{"key":"2025032907470920100_R57","first-page":"7075","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032907470920100_R58","first-page":"6045","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032907470920100_R59","first-page":"503","volume-title":"J. Exp. 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