{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:49:12Z","timestamp":1791114552352,"version":"4.1.0"},"reference-count":45,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,5,17]]},"abstract":"<jats:p>The Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 contains a glycine-alanine repeat (GAr) domain that appears to protect the antigen from proteasomal breakdown and, as measured in cytotoxicity assays, from major histocompatibility complex (MHC) class I\u2013restricted presentation to CD8+ T cells. This led to the concept of EBNA1 as an immunologically silent protein that although unique in being expressed in all EBV malignancies, could not be exploited as a CD8 target. Here, using CD8+ T cell clones to native EBNA1 epitopes upstream and downstream of the GAr domain and assaying recognition by interferon \u03b3 release, we show that the EBNA1 naturally expressed in EBV-transformed lymphoblastoid cell lines (LCLs) is in fact presented to CD8+ T cells via a proteasome\/peptide transporter\u2013dependent pathway. Furthermore, LCL recognition by such CD8+ T cells, although slightly lower than seen with paired lines expressing a GAr-deleted EBNA1 protein, leads to strong and specific inhibition of LCL outgrowth in vitro. Endogenously expressed EBNA1 is therefore accessible to the MHC class I pathway despite GAr-mediated stabilization of the mature protein. We infer that EBNA1-specific CD8+ T cells do play a role in control of EBV infection in vivo and might be exploitable in the control of EBV+ malignancies.<\/jats:p>","DOI":"10.1084\/jem.20040121","type":"journal-article","created":{"date-parts":[[2004,5,17]],"date-time":"2004-05-17T18:43:01Z","timestamp":1084819381000},"page":"1409-1420","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":138,"title":["CD8 T Cell Recognition of Endogenously Expressed Epstein-Barr Virus Nuclear Antigen 1"],"prefix":"10.1084","volume":"199","author":[{"given":"Steven P.","family":"Lee","sequence":"first","affiliation":[{"name":"1Institute for Cancer Studies, The University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Brooks","sequence":"additional","affiliation":[{"name":"1Institute for Cancer Studies, The University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatim","family":"Al-Jarrah","sequence":"additional","affiliation":[{"name":"2Department of Medical Microbiology, University of Liverpool, Liverpool L69 36A, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Thomas","sequence":"additional","affiliation":[{"name":"1Institute for Cancer Studies, The University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey A.","family":"Haigh","sequence":"additional","affiliation":[{"name":"1Institute for Cancer Studies, The University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham S.","family":"Taylor","sequence":"additional","affiliation":[{"name":"1Institute for Cancer Studies, The University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibille","family":"Humme","sequence":"additional","affiliation":[{"name":"3Department of Gene Vectors, GSF-National Research Centre for Environment and Health, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aloys","family":"Schepers","sequence":"additional","affiliation":[{"name":"3Department of Gene Vectors, GSF-National Research Centre for Environment and Health, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hammerschmidt","sequence":"additional","affiliation":[{"name":"3Department of Gene Vectors, GSF-National Research Centre for Environment and Health, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Yates","sequence":"additional","affiliation":[{"name":"4Department of Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan B.","family":"Rickinson","sequence":"additional","affiliation":[{"name":"1Institute for Cancer Studies, The University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil W.","family":"Blake","sequence":"additional","affiliation":[{"name":"2Department of Medical Microbiology, University of Liverpool, Liverpool L69 36A, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2004,5,17]]},"reference":[{"key":"2023072512202654500_BIB1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev.immunol.16.1.323","volume":"16","year":"1998","journal-title":"Annu. 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