{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:22:18Z","timestamp":1790853738410,"version":"4.1.0"},"reference-count":33,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,2,16]]},"abstract":"<jats:p>The Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) is expressed in all EBV-associated tumors, making it an important target for immunotherapy. However, evidence for major histocompatibility complex (MHC) class I\u2013restricted EBNA1 peptides endogenously presented by EBV-transformed B and tumor cells remains elusive. Here we describe for the first time the identification of an endogenously processed human histocompatibility leukocyte antigen (HLA)-B8\u2013restricted EBNA1 peptide that is recognized by CD8+ T cells. T cell recognition could be inhibited by the treatment of target cells with proteasome inhibitors that block the MHC class I antigen processing pathway, but not by an inhibitor (chloroquine) of MHC class II antigen processing. We also demonstrate that new protein synthesis is required for the generation of the HLA-B8 epitope for T cell recognition, suggesting that defective ribosomal products (DRiPs) are the major source of T cell epitopes. Experiments with protease inhibitors indicate that some serine proteases may participate in the degradation of EBNA1 DRiPs before they are further processed by proteasomes. These findings not only provide the first evidence of the presentation of an MHC class I\u2013restricted EBNA1 epitope to CD8+ T cells, but also offer new insight into the molecular mechanisms involved in the processing and presentation of EBNA1.<\/jats:p>","DOI":"10.1084\/jem.20031219","type":"journal-article","created":{"date-parts":[[2004,2,10]],"date-time":"2004-02-10T01:45:07Z","timestamp":1076377507000},"page":"459-470","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":130,"title":["Evidence for the Presentation of Major Histocompatibility Complex Class I\u2013restricted Epstein-Barr Virus Nuclear Antigen 1 Peptides to CD8+ T Lymphocytes"],"prefix":"10.1084","volume":"199","author":[{"given":"Kui Shin","family":"Voo","sequence":"first","affiliation":[{"name":"1Department of Immunology, The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tihui","family":"Fu","sequence":"additional","affiliation":[{"name":"1Department of Immunology, The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Immunology, The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Tellam","sequence":"additional","affiliation":[{"name":"3Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, University of Queensland, Brisbane, Queensland 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen E.","family":"Heslop","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm K.","family":"Brenner","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cliona M.","family":"Rooney","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Fu","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Immunology, The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2004,2,9]]},"reference":[{"key":"2023072512291261600_BIB1","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1056\/NEJM199509143331110","volume":"333","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"2023072512291261600_BIB2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.immunol.15.1.405","volume":"15","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"2023072512291261600_BIB3","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1002\/j.1460-2075.1987.tb02568.x","volume":"6","year":"1987","journal-title":"EMBO J."},{"key":"2023072512291261600_BIB4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1600-065X.1999.tb01328.x","volume":"170","year":"1999","journal-title":"Immunol. Rev."},{"key":"2023072512291261600_BIB5","doi-asserted-by":"crossref","first-page":"7078","DOI":"10.4049\/jimmunol.165.12.7078","volume":"165","year":"2000","journal-title":"J. Immunol."},{"key":"2023072512291261600_BIB6","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/375685a0","volume":"375","year":"1995","journal-title":"Nature."},{"key":"2023072512291261600_BIB7","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S1074-7613(00)80397-0","volume":"7","year":"1997","journal-title":"Immunity."},{"key":"2023072512291261600_BIB8","doi-asserted-by":"crossref","first-page":"12616","DOI":"10.1073\/pnas.94.23.12616","volume":"94","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072512291261600_BIB9","doi-asserted-by":"crossref","first-page":"8649","DOI":"10.1128\/JVI.75.18.8649-8659.2001","volume":"75","year":"2001","journal-title":"J. Virol."},{"key":"2023072512291261600_BIB10","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.4049\/jimmunol.169.3.1593","volume":"169","year":"2002","journal-title":"J. Immunol."},{"key":"2023072512291261600_BIB11","first-page":"7195","volume":"62","year":"2002","journal-title":"Cancer Res."},{"key":"2023072512291261600_BIB12","doi-asserted-by":"crossref","first-page":"3596","DOI":"10.4049\/jimmunol.161.7.3596","volume":"161","year":"1998","journal-title":"J. Immunol."},{"key":"2023072512291261600_BIB13","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1084\/jem.183.3.1131","volume":"183","year":"1996","journal-title":"J. Exp. Med."},{"key":"2023072512291261600_BIB14","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.4049\/jimmunol.162.3.1827","volume":"162","year":"1999","journal-title":"J. Immunol."},{"key":"2023072512291261600_BIB15","doi-asserted-by":"crossref","first-page":"33353","DOI":"10.1074\/jbc.M104535200","volume":"276","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2023072512291261600_BIB16","first-page":"3519","volume":"58","year":"1998","journal-title":"Cancer Res."},{"key":"2023072512291261600_BIB17","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1126\/science.284.5418.1351","volume":"284","year":"1999","journal-title":"Science."},{"key":"2023072512291261600_BIB18","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1084\/jem.191.10.1649","volume":"191","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072512291261600_BIB19","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/ijc.1503","volume":"94","year":"2001","journal-title":"Int. J. Cancer."},{"key":"2023072512291261600_BIB20","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev.immunol.19.1.47","volume":"19","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"2023072512291261600_BIB21","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1600-065X.1999.tb01331.x","volume":"170","year":"1999","journal-title":"Immunol. Rev."},{"key":"2023072512291261600_BIB22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2776(02)80012-8","volume":"80","year":"2002","journal-title":"Adv. Immunol."},{"key":"2023072512291261600_BIB23","doi-asserted-by":"crossref","first-page":"10326","DOI":"10.1073\/pnas.96.18.10326","volume":"96","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072512291261600_BIB24","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0092-8674(94)90336-0","volume":"76","year":"1994","journal-title":"Cell."},{"key":"2023072512291261600_BIB25","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/35008096","volume":"404","year":"2000","journal-title":"Nature."},{"key":"2023072512291261600_BIB26","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/35008103","volume":"404","year":"2000","journal-title":"Nature."},{"key":"2023072512291261600_BIB27","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1242\/jcs.114.5.845","volume":"114","year":"2001","journal-title":"J. Cell Sci."},{"key":"2023072512291261600_BIB28","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S1471-4906(01)01860-9","volume":"22","year":"2001","journal-title":"Trends Immunol."},{"key":"2023072512291261600_BIB29","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1006\/viro.1995.0076","volume":"214","year":"1995","journal-title":"Virology."},{"key":"2023072512291261600_BIB30","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1089\/088282402317340350","volume":"15","year":"2002","journal-title":"Viral Immunol."},{"key":"2023072512291261600_BIB31","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1182\/blood-2002-03-0791","volume":"101","year":"2003","journal-title":"Blood."},{"key":"2023072512291261600_BIB32","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S1471-4906(01)01896-8","volume":"22","year":"2001","journal-title":"Trends Immunol."},{"key":"2023072512291261600_BIB33","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1126\/science.1088902","volume":"301","year":"2003","journal-title":"Science."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/199\/4\/459\/1713650\/jem1994459.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/199\/4\/459\/1713650\/jem1994459.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T12:39:55Z","timestamp":1690288795000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/199\/4\/459\/40087\/Evidence-for-the-Presentation-of-Major"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,2,9]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,2,16]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20031219","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2004,2,9]]}}}