{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T11:32:36Z","timestamp":1791718356969,"version":"4.3.4"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2000,6,1]],"date-time":"2000-06-01T00:00:00Z","timestamp":959817600000},"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":[[2000,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The complete inhibition of proteasome activities interferes with the production of most MHC class I peptide ligands as well as with cellular proliferation and survival. In this study we have investigated how partial and selective inhibition of the chymotrypsin-like activity of the proteasome by the proteasome inhibitors lactacystin or epoxomicin would affect Ag presentation. At 0.5\u20131 \u03bcM lactacystin, the presentation of the lymphocytic choriomeningitis virus-derived epitopes NP118 and GP33 and the mouse CMV epitope pp89\u2013168 were reduced and were further diminished in a dose-dependent manner with increasing concentrations. Presentation of the lymphocytic choriomeningitis virus-derived epitope GP276, in contrast, was markedly enhanced at low, but abrogated at higher, concentrations of either lactacystin or epoxomicin. The inhibitor-mediated effects were thus epitope specific and did not correlate with the degradation rates of the involved viral proteins. Although neither apoptosis induction nor interference with cellular proliferation was observed at 0.5\u20131 \u03bcM lactacystin in vivo, this concentration was sufficient to alter the fragmentation of polypeptides by the 20S proteasome in vitro. Our results indicate that partial and selective inhibition of proteasome activity in vivo is a valid approach to modulate Ag presentation, with potential applications for the treatment of autoimmune diseases and the prevention of transplant rejection.<\/jats:p>","DOI":"10.4049\/jimmunol.164.12.6147","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:59:29Z","timestamp":1398031169000},"page":"6147-6157","source":"Crossref","is-referenced-by-count":82,"title":["The Selective Proteasome Inhibitors Lactacystin and Epoxomicin Can Be Used to Either Up- or Down-Regulate Antigen Presentation at Nontoxic Doses"],"prefix":"10.1093","volume":"164","author":[{"given":"Katrin","family":"Schwarz","sequence":"first","affiliation":[{"name":"Research Department, Cantonal Hospital St. Gall , St. Gallen ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"de Giuli","sequence":"additional","affiliation":[{"name":"Research Department, Cantonal Hospital St. Gall , St. Gallen ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunter","family":"Schmidtke","sequence":"additional","affiliation":[{"name":"Research Department, Cantonal Hospital St. Gall , St. Gallen ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Kostka","sequence":"additional","affiliation":[{"name":"Max Delbru\u0308ck Center for Molecular Medicine , Berlin-Buch ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maries","family":"van den Broek","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Bo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, Yale University , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M","family":"Crews","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, Yale University , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regine","family":"Kraft","sequence":"additional","affiliation":[{"name":"Max Delbru\u0308ck Center for Molecular Medicine , Berlin-Buch ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Groettrup","sequence":"additional","affiliation":[{"name":"Research Department, Cantonal Hospital St. Gall , St. Gallen ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,6,15]]},"reference":[{"key":"2026020214041052400_R1","first-page":"739","volume-title":"Annu. 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