{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:56:46Z","timestamp":1791341806435,"version":"4.3.1"},"reference-count":65,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,5,15]]},"abstract":"<jats:p>The Epstein-Barr virus (EBV)-encoded nuclear antigen EBNA1 is critical for the persistence of the viral episome in replicating EBV-transformed human B cells. Therefore, all EBV-induced tumors express this foreign antigen. However, EBNA1 is invisible to CD8+ cytotoxic T lymphocytes because its Gly\/Ala repeat domain prevents proteasome-dependent processing for presentation on major histocompatibility complex (MHC) class I. We now describe that CD4+ T cells from healthy adults are primed to EBNA1. In fact, among latent EBV antigens that stimulate CD4+ T cells, EBNA1 is preferentially recognized. We present evidence that the CD4+ response may provide a protective role, including interferon \u03b3 secretion and direct cytolysis after encounter of transformed B lymphocyte cell lines (B-LCLs). Dendritic cells (DCs) process EBNA1 from purified protein and from MHC class II\u2013mismatched, EBNA1-expressing cells including B-LCLs. In contrast, B-LCLs and Burkitt's lymphoma lines likely present EBNA1 after endogenous processing, as their capacity to cross-present from exogenous sources is weak or undetectable. By limiting dilution, there is a tight correlation between the capacity of CD4+ T cell lines to recognize autologous B-LCL\u2013expressing EBNA1 and DCs that have captured EBNA1. Therefore, CD4+ T cells can respond to the EBNA1 protein that is crucial for EBV persistence. We suggest that this immune response is initiated in vivo by DCs that present EBV-infected B cells, and that EBNA1-specific CD4+ T cell immunity be enhanced to prevent and treat EBV-associated malignancies.<\/jats:p>","DOI":"10.1084\/jem.191.10.1649","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1649-1660","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":295,"title":["Human Cd4+ T Lymphocytes Consistently Respond to the Latent Epstein-Barr Virus Nuclear Antigen Ebna1"],"prefix":"10.1084","volume":"191","author":[{"given":"Christian","family":"M\u00fcnz","sequence":"first","affiliation":[{"name":"aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara L.","family":"Bickham","sequence":"additional","affiliation":[{"name":"aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Subklewe","sequence":"additional","affiliation":[{"name":"aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming L.","family":"Tsang","sequence":"additional","affiliation":[{"name":"aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Chahroudi","sequence":"additional","affiliation":[{"name":"aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Kurilla","sequence":"additional","affiliation":[{"name":"cDepartment of Pathology and Microbiology, University of Virginia, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[{"name":"bLaboratory of DNA Replication and Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021-6399"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"bLaboratory of DNA Replication and Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021-6399"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph M.","family":"Steinman","sequence":"additional","affiliation":[{"name":"aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,5,8]]},"reference":[{"key":"2023072509032574800_R1","first-page":"2343","article-title":"Epstein-Barr virus and its replication","volume-title":"Virology","author":"Kieff","year":"1996"},{"key":"2023072509032574800_R2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/0092-8674(94)90125-2","article-title":"Epstein-Barr virus strategy in normal and neoplastic B cells","volume":"77","author":"Klein","year":"1994","journal-title":"Cell."},{"key":"2023072509032574800_R3","first-page":"2397","article-title":"Epstein-Barr virus","volume-title":"Virology","author":"Rickinson","year":"1996"},{"key":"2023072509032574800_R4","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/349612a0","article-title":"Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis","volume":"349","author":"Gregory","year":"1991","journal-title":"Nature."},{"key":"2023072509032574800_R5","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S0092-8674(00)81056-9","article-title":"Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin-binding protein, EBNA1, bound to DNA","volume":"84","author":"Bochkarev","year":"1996","journal-title":"Cell."},{"key":"2023072509032574800_R6","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1128\/jvi.66.6.3355-3362.1992","article-title":"Binding of EBNA-1 to DNA creates a protease-resistant domain that encompasses the DNA recognition and dimerization functions","volume":"66","author":"Shah","year":"1992","journal-title":"J. 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