{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:47:16Z","timestamp":1773658036377,"version":"3.50.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2002,7,1]],"date-time":"2002-07-01T00:00:00Z","timestamp":1025481600000},"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":[[2002,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In this study we demonstrate that a disarmed version of the cytotoxin ricin can deliver exogenous CD8+ T cell epitopes into the MHC class I-restricted pathway by a TAP-independent, signal peptidase-dependent pathway. Defined viral peptide epitopes genetically fused to the N terminus of an attenuated ricin A subunit (RTA) that was reassociated with its partner B subunit were able to reach the early secretory pathway of sensitive cells, including TAP-deficient cells. Successful processing and presentation by MHC class I proteins was not dependent on proteasome activity or on recycling of MHC class I proteins, but rather on a functional secretory pathway. Our results demonstrated a role for signal peptidase in the generation of peptide epitopes associated at the amino terminus of RTA. We showed, first, that potential signal peptide cleavage sites located toward the N terminus of RTA can be posttranslationally cleaved by signal peptidase and, second, that mutation of one of these sites led to a loss of peptide presentation. These results identify a novel MHC class I presentation pathway that exploits the ability of toxins to reach the lumen of the endoplasmic reticulum by retrograde transport, and suggest a role for endoplasmic reticulum signal peptidase in the processing and presentation of MHC class I peptides. Because TAP-negative cells can be sensitized for CTL killing following retrograde transport of toxin-linked peptides, application of these results has direct implications for the development of novel vaccination strategies.<\/jats:p>","DOI":"10.4049\/jimmunol.169.1.99","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:33:01Z","timestamp":1398025981000},"page":"99-107","source":"Crossref","is-referenced-by-count":19,"title":["Exogenous Peptides Delivered by Ricin Require Processing by Signal Peptidase for Transporter Associated with Antigen Processing-Independent MHC Class I-Restricted Presentation"],"prefix":"10.1093","volume":"169","author":[{"given":"Daniel C","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Warwick , Coventry ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Awen","family":"Gallimore","sequence":"additional","affiliation":[{"name":"Molecular Immunology Group, Nuffield Department of Medicine, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Jones","sequence":"additional","affiliation":[{"name":"Molecular Immunology Group, Nuffield Department of Medicine, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Warwick , Coventry ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J Michael","family":"Lord","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Warwick , Coventry ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Deeks","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Warwick , Coventry ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Cerundolo","sequence":"additional","affiliation":[{"name":"Molecular Immunology Group, Nuffield Department of Medicine, John Radcliffe Hospital , Oxford ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynne M","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Warwick , Coventry ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,7,1]]},"reference":[{"key":"2026020208182776600_R1","first-page":"126","volume-title":"Immunol. 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Res.","year":"1983"},{"key":"2026020208182776600_R11","first-page":"51","volume-title":"Molecular Action of Toxins and Viruses","year":"1982"},{"key":"2026020208182776600_R12","first-page":"510","volume-title":"Nature","year":"1992"},{"key":"2026020208182776600_R13","first-page":"20078","volume-title":"J. Biol. Chem.","year":"1995"},{"key":"2026020208182776600_R14","first-page":"3783","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2026020208182776600_R15","first-page":"507","volume-title":"Semin. Cell Dev. Biol.","year":"1999"},{"key":"2026020208182776600_R16","first-page":"80","volume-title":"FEBS Lett.","year":"1999"},{"key":"2026020208182776600_R17","first-page":"23","volume-title":"Int. J. 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Biol.","year":"1993"},{"key":"2026020208182776600_R26","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1007\/978-94-010-9063-6_34","volume-title":"Proteins","year":"1991"},{"key":"2026020208182776600_R27","first-page":"76","volume-title":"Curr. Opin. Immunol.","year":"1999"},{"key":"2026020208182776600_R28","first-page":"13944","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1999"},{"key":"2026020208182776600_R29","first-page":"1105","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020208182776600_R30","first-page":"641","volume-title":"Traffic","year":"2000"},{"key":"2026020208182776600_R31","first-page":"119","volume-title":"Microbiol. 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