{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:07:06Z","timestamp":1791288426562,"version":"4.3.0"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,3]]},"abstract":"<jats:p>\n                    The Epstein\u2013Barr virus (EBV) nuclear antigen-1 (EBNA-1) is potentially a universal target for immune recognition of EBV-infected normal or malignant cells. EBNA-1-specific CD8+ T-cell responses have been assessed against a few epitopes presented on a limited number of HLA class I alleles. We now assess CD8+ T-cell responses to a complete panel of EBNA-1 peptides in an HLA-characterized population. We detected EBNA-1-specific CD8+ T cells in 10 of 14 healthy donors by analysis of peripheral blood mononuclear cells and EBV-specific T-cell lines. The frequent detection of CD8+ T-cell responses was confirmed by mapping EBNA-1 epitopes and demonstrating HLA class I presentation to CD8+ T cells in 6 of 6 donors, including 2 new EBNA-1 epitopes presented by HLA A0206 and A6802. Importantly, EBNA-1-specific CD8+ T cells were significantly less frequent in EBV-specific T-cell lines from patients with EBV-associated nasopharyngeal carcinoma (3 out of 22,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0003), whereas the frequency of LMP2-specific responses (14 out of 22) was not significantly different from healthy donors (11 out of 14). EBNA-1-specific CD8+ T-cell responses were rescued in approximately half of nasopharyngeal carcinoma patients by peptide and cytokine stimulation of peripheral blood mononuclear cells, suggesting these EBNA-1-specific CD8+ T cells were functionally defective in their response to EBV-infected cells. These results indicate that humans normally mount a significant EBNA-1-specific CD8+ T-cell response to EBV infection, but the immune response to this tumor antigen has been significantly altered in nasopharyngeal carcinoma patients. Overcoming this defect in EBV-specific immunity may prevent or enhance treatment of EBV-associated nasopharyngeal carcinoma.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0813320106","type":"journal-article","created":{"date-parts":[[2009,2,11]],"date-time":"2009-02-11T21:36:12Z","timestamp":1234388172000},"page":"3318-3323","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":50,"title":["Decreased EBNA-1-specific CD8+ T cells in patients with Epstein\u2013Barr virus-associated nasopharyngeal carcinoma"],"prefix":"10.1073","volume":"106","author":[{"given":"Mark H.","family":"Fogg","sequence":"first","affiliation":[{"name":"Department of Medicine, Brigham and Women's Hospital, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori J.","family":"Wirth","sequence":"additional","affiliation":[{"name":"Department of Adult Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall","family":"Posner","sequence":"additional","affiliation":[{"name":"Department of Adult Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women's Hospital, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdf179"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1569"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199601)178:1<44::AID-PATH471>3.0.CO;2-0"},{"key":"e_1_3_3_4_2","first-page":"879","article-title":"Expression of Epstein-Barr virus genes and of lymphocyte activation molecules in undifferentiated nasopharyngeal carcinomas","volume":"140","author":"Niedobitek G","year":"1992","unstructured":"G Niedobitek, et al., Expression of Epstein-Barr virus genes and of lymphocyte activation molecules in undifferentiated nasopharyngeal carcinomas. 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