Human Cd4+ T Lymphocytes Consistently Respond to the Latent Epstein-Barr Virus Nuclear Antigen Ebna1
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- Christian Münz
- aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399
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- Kara L. Bickham
- aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399
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- Marion Subklewe
- aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399
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- Ming L. Tsang
- aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399
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- Ann Chahroudi
- aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399
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- Michael G. Kurilla
- cDepartment of Pathology and Microbiology, University of Virginia, Charlottesville, Virginia 22908
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- Dan Zhang
- bLaboratory of DNA Replication and Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021-6399
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- Michael O'Donnell
- bLaboratory of DNA Replication and Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021-6399
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- Ralph M. Steinman
- aLaboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399
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<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 γ 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–mismatched, 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–expressing 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>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 191 (10), 1649-1660, 2000-05-08
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1361137046342859264
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- NII論文ID
- 30017414986
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- NII書誌ID
- AA00697559
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- ISSN
- 15409538
- 00221007
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