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*
Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom; and
Clinical Research Center Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom
EBV is a gammaherpesvirus that can establish both nonproductive (latent) and productive (lytic) infections within the cells of its host. Although T cell responses to EBV latent proteins have been well characterized, little is known about the importance of responses to lytic proteins in long term virus carriers. Here we have compared the frequencies of CD8+ T cells specific for EBV latent and lytic Ags in healthy virus carriers, using three techniques: limiting dilution analysis, enzyme-linked immunospot assay, and FACS staining with tetrameric MHC-peptide complexes. T cells specific for EBV lytic protein epitopes were readily detectable in all donors and were usually more abundant than those specific for latent epitopes. We infer that direct T cell control of viral replicative lesions is maintained in long term carriers of EBV and is an important component of the immune response to this virus. Estimates of CD8+ T cell frequencies varied considerably according to methodology; values obtained from MHC-peptide tetramer staining were, on the average, 4.4-fold higher than those obtained from enzyme-linked immunospot assays, which were, in turn, on the average, 5.3-fold higher than those obtained from limiting dilution analysis. Tetramer staining showed that as many as 5.5% circulating CD8+ T cells in a virus carrier were specific for a single EBV lytic protein epitope. Such values are much greater than previously imagined and illustrate how antigenic challenge from a persistent herpesvirus can influence the composition of the host’s CD8+ T cell pool.
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 A. R. Gordon, L. A. Loevner, A. I. Sonners, W. E. Bolger, and M. A. Wasik Posttransplantation Lymphoproliferative Disorder of the Paranasal Sinuses Mimicking Invasive Fungal Sinusitis: Case Report AJNR Am. J. Neuroradiol., May 1, 2002; 23(5): 855 - 857. [Abstract] [Full Text] [PDF]
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Q. J. Wang, X.-L. Huang, G. Rappocciolo, F. J. Jenkins, W. H. Hildebrand, Z. Fan, E. K. Thomas, and C. R. Rinaldo Jr Identification of an HLA A*0201-restricted CD8+ T-cell epitope for the glycoprotein B homolog of human herpesvirus 8 Blood, May 1, 2002; 99(9): 3360 - 3366. [Abstract] [Full Text] [PDF]
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M. D. Catalina, J. L. Sullivan, R. M. Brody, and K. Luzuriaga Phenotypic and Functional Heterogeneity of EBV Epitope-Specific CD8+ T Cells J. Immunol., April 15, 2002; 168(8): 4184 - 4191. [Abstract] [Full Text] [PDF]
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M. P. Davenport, C. Fazou, A. J. McMichael, and M. F. C. Callan Clonal Selection, Clonal Senescence, and Clonal Succession: The Evolution of the T Cell Response to Infection with a Persistent Virus J. Immunol., April 1, 2002; 168(7): 3309 - 3317. [Abstract] [Full Text] [PDF]
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S. Kostense, K. Vandenberghe, J. Joling, D. Van Baarle, N. Nanlohy, E. Manting, and F. Miedema Persistent numbers of tetramer+ CD8+ T cells, but loss of interferon-gamma + HIV-specific T cells during progression to AIDS Blood, April 1, 2002; 99(7): 2505 - 2511. [Abstract] [Full Text] [PDF]
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F. Mattner, J.-K. Fleitmann, K. Lingnau, W. Schmidt, A. Egyed, J. Fritz, W. Zauner, B. Wittmann, I. Gorny, M. Berger, et al. Vaccination with Poly-L-Arginine As Immunostimulant for Peptide Vaccines: Induction of Potent and Long-Lasting T-Cell Responses against Cancer Antigens Cancer Res., March 1, 2002; 62(5): 1477 - 1480. [Abstract] [Full Text] [PDF]
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G. Koehne, K. M. Smith, T. L. Ferguson, R. Y. Williams, G. Heller, E. G. Pamer, B. Dupont, and R. J. O'Reilly Quantitation, selection, and functional characterization of Epstein-Barr virus-specific and alloreactive T cells detected by intracellular interferon-gamma production and growth of cytotoxic precursors Blood, March 1, 2002; 99(5): 1730 - 1740. [Abstract] [Full Text] [PDF]
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D. Sauce, M. Bodinier, M. Garin, B. Petracca, N. Tonnelier, A. Duperrier, J. V. Melo, J. F. Apperley, C. Ferrand, P. Herve, et al. Retrovirus-mediated gene transfer in primary T lymphocytes impairs their anti-Epstein-Barr virus potential through both culture-dependent and selection process-dependent mechanisms Blood, February 15, 2002; 99(4): 1165 - 1173. [Abstract] [Full Text] [PDF]
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 E. G.-T. Wee, S. Patel, A. J. McMichael, and T. Hanke A DNA/MVA-based candidate human immunodeficiency virus vaccine for Kenya induces multi-specific T cell responses in rhesus macaques J. Gen. Virol., January 1, 2002; 83(1): 75 - 80. [Abstract] [Full Text] [PDF]
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T. U. Vogel, B. E. Beer, J. zur Megede, H.-G. Ihlenfeldt, G. Jung, S. Holzammer, D. I. Watkins, J. D. Altman, R. Kurth, and S. Norley Induction of anti-simian immunodeficiency virus cellular and humoral immune responses in rhesus macaques by peptide immunogens: correlation of CTL activity and reduction of cell-associated but not plasma virus load following challenge J. Gen. Virol., January 1, 2002; 83(1): 81 - 91. [Abstract] [Full Text] [PDF]
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K. Peggs, S. Verfuerth, A. Pizzey, J. Ainsworth, P. Moss, and S. Mackinnon Characterization of human cytomegalovirus peptide-specific CD8+ T-cell repertoire diversity following in vitro restimulation by antigen-pulsed dendritic cells Blood, January 1, 2002; 99(1): 213 - 223. [Abstract] [Full Text] [PDF]
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 A. Ascherio, K. L. Munger, E. T. Lennette, D. Spiegelman, M. A. Hernan, M. J. Olek, S. E. Hankinson, and D. J. Hunter Epstein-Barr Virus Antibodies and Risk of Multiple Sclerosis: A Prospective Study JAMA, December 26, 2001; 286(24): 3083 - 3088. [Abstract] [Full Text] [PDF]
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A. A. Pathan, K. A. Wilkinson, P. Klenerman, H. McShane, R. N. Davidson, G. Pasvol, A. V. S. Hill, and A. Lalvani Direct Ex Vivo Analysis of Antigen-Specific IFN-{gamma}-Secreting CD4 T Cells in Mycobacterium tuberculosis-Infected Individuals: Associations with Clinical Disease State and Effect of Treatment J. Immunol., November 1, 2001; 167(9): 5217 - 5225. [Abstract] [Full Text] [PDF]
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G. Gallot, R. Vivien, C. Ibisch, J. Lule, C. Davrinche, J. Gaschet, and H. Vie Purification of Ag-Specific T Lymphocytes After Direct Peripheral Blood Mononuclear Cell Stimulation Followed by CD25 Selection. I. Application to CD4+ or CD8+ Cytomegalovirus Phosphoprotein pp65 Epitope Determination J. Immunol., October 15, 2001; 167(8): 4196 - 4206. [Abstract] [Full Text] [PDF]
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M. D. Catalina, J. L. Sullivan, K. R. Bak, and K. Luzuriaga Differential Evolution and Stability of Epitope-Specific CD8+ T Cell Responses in EBV Infection J. Immunol., October 15, 2001; 167(8): 4450 - 4457. [Abstract] [Full Text] [PDF]
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W. Kuon, H.-G. Holzhutter, H. Appel, M. Grolms, S. Kollnberger, A. Traeder, P. Henklein, E. Weiss, A. Thiel, R. Lauster, et al. Identification of HLA-B27-Restricted Peptides from the Chlamydia trachomatis Proteome with Possible Relevance to HLA-B27-Associated Diseases J. Immunol., October 15, 2001; 167(8): 4738 - 4746. [Abstract] [Full Text] [PDF]
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A. Leen, P. Meij, I. Redchenko, J. Middeldorp, E. Bloemena, A. Rickinson, and N. Blake Differential Immunogenicity of Epstein-Barr Virus Latent-Cycle Proteins for Human CD4+ T-Helper 1 Responses J. Virol., September 15, 2001; 75(18): 8649 - 8659. [Abstract] [Full Text] [PDF]
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A. D. Hislop, N. H. Gudgeon, M. F. C. Callan, C. Fazou, H. Hasegawa, M. Salmon, and A. B. Rickinson EBV-Specific CD8+ T Cell Memory: Relationships Between Epitope Specificity, Cell Phenotype, and Immediate Effector Function J. Immunol., August 15, 2001; 167(4): 2019 - 2029. [Abstract] [Full Text] [PDF]
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A. L. N. Chapman, A. B. Rickinson, W. A. Thomas, R. F. Jarrett, J. Crocker, and S. P. Lee Epstein-Barr Virus-specific Cytotoxic T Lymphocyte Responses in the Blood and Tumor Site of Hodgkin's Disease Patients: Implications for a T-cell-based Therapy Cancer Res., August 1, 2001; 61(16): 6219 - 6226. [Abstract] [Full Text] [PDF]
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C. S. Gricks, E. Rawlings, L. Foroni, J. A. Madrigal, and P. L. Amlot Somatically Mutated Regions of Immunoglobulin on Human B-Cell Lymphomas Code for Peptides That Bind to Autologous Major Histocompatibility Complex Class I, Providing a Potential Target for Cytotoxic T Cells Cancer Res., July 1, 2001; 61(13): 5145 - 5152. [Abstract] [Full Text] [PDF]
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D. van Baarle, E. Hovenkamp, M. F. C. Callan, K. C. Wolthers, S. Kostense, L. C. Tan, H. G. M. Niesters, A. D. M. E. Osterhaus, A. J. McMichael, M. H. J. van Oers, et al. Dysfunctional Epstein-Barr virus (EBV)-specific CD8+ T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma Blood, July 1, 2001; 98(1): 146 - 155. [Abstract] [Full Text] [PDF]
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E. J. Novak, A. W. Liu, J. A. Gebe, B. A. Falk, G. T. Nepom, D. M. Koelle, and W. W. Kwok Tetramer-Guided Epitope Mapping: Rapid Identification and Characterization of Immunodominant CD4+ T Cell Epitopes from Complex Antigens J. Immunol., June 1, 2001; 166(11): 6665 - 6670. [Abstract] [Full Text] [PDF]
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T. M. Clay, A. C. Hobeika, P. J. Mosca, H. K. Lyerly, and M. A. Morse Assays for Monitoring Cellular Immune Responses to Active Immunotherapy of Cancer Clin. Cancer Res., May 1, 2001; 7(5): 1127 - 1135. [Abstract] [Full Text]
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V. Monsurro, M.-B. Nielsen, A. Perez-Diez, M. E. Dudley, E. Wang, S. A. Rosenberg, and F. M. Marincola Kinetics of TCR Use in Response to Repeated Epitope-Specific Immunization J. Immunol., May 1, 2001; 166(9): 5817 - 5825. [Abstract] [Full Text] [PDF]
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S. Nikiforow, K. Bottomly, and G. Miller CD4+ T-Cell Effectors Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation J. Virol., April 15, 2001; 75(8): 3740 - 3752. [Abstract] [Full Text]
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Q. J. Wang, F. J. Jenkins, L. P. Jacobson, L. A. Kingsley, R. D. Day, Z.-W. Zhang, Y.-X. Meng, P. E. Pellet, K. G. Kousoulas, A. Baghian, et al. Primary human herpesvirus 8 infection generates a broadly specific CD8+ T-cell response to viral lytic cycle proteins Blood, April 15, 2001; 97(8): 2366 - 2373. [Abstract] [Full Text] [PDF]
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C. Rose, M. Green, S. Webber, D. Ellis, J. Reyes, and D. Rowe Pediatric Solid-Organ Transplant Recipients Carry Chronic Loads of Epstein-Barr Virus Exclusively in the Immunoglobulin D-Negative B-Cell Compartment J. Clin. Microbiol., April 1, 2001; 39(4): 1407 - 1415. [Abstract] [Full Text]
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K. Cwynarski, J. Ainsworth, M. Cobbold, S. Wagner, P. Mahendra, J. Apperley, J. Goldman, C. Craddock, and P. A. H. Moss Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation Blood, March 1, 2001; 97(5): 1232 - 1240. [Abstract] [Full Text] [PDF]
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P. J. R. Goulder, , M. M. Addo, M. A. Altfeld, E. S. Rosenberg, Y. Tang, U. Govender, N. Mngqundaniso, K. Annamalai, T. U. Vogel, M. Hammond, et al. Rapid Definition of Five Novel HLA-A*3002-Restricted Human Immunodeficiency Virus-Specific Cytotoxic T-Lymphocyte Epitopes by Elispot and Intracellular Cytokine Staining Assays J. Virol., February 1, 2001; 75(3): 1339 - 1347. [Abstract] [Full Text]
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P. J.R. Goulder, M. A. Altfeld, E. S. Rosenberg, T. Nguyen, Y. Tang, R. L. Eldridge, M. M. Addo, S. He, J. S. Muckerjee, M. N. Phillips, et al. Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection J. Exp. Med., January 15, 2001; 193(2): 181 - 194. [Abstract] [Full Text] [PDF]
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T. O. Cameron, J. R. Cochran, B. Yassine-Diab, R.-P. Sekaly, and L. J. Stern Cutting Edge: Detection of Antigen-Specific CD4+ T Cells by HLA-DR1 Oligomers Is Dependent on the T Cell Activation State J. Immunol., January 15, 2001; 166(2): 741 - 745. [Abstract] [Full Text] [PDF]
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P. J.R. Goulder, Y. Tang, C. Brander, M. R. Betts, M. Altfeld, K. Annamalai, A. Trocha, S. He, E. S. Rosenberg, G. Ogg, et al. Functionally Inert HIV-Specific Cytotoxic T Lymphocytes Do Not Play a Major Role in Chronically Infected Adults and Children J. Exp. Med., December 18, 2000; 192(12): 1819 - 1832. [Abstract] [Full Text] [PDF]
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S. M. Smith, R. Brookes, M. R. Klein, A. S. Malin, P. T. Lukey, A. S. King, G. S. Ogg, A. V. S. Hill, and H. M. Dockrell Human CD8+ CTL Specific for the Mycobacterial Major Secreted Antigen 85A J. Immunol., December 15, 2000; 165(12): 7088 - 7095. [Abstract] [Full Text] [PDF]
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S.-K. Kim, L. Devine, M. Angevine, R. DeMars, and P. B. Kavathas Direct Detection and Magnetic Isolation of Chlamydia trachomatis Major Outer Membrane Protein-Specific CD8+ CTLs with HLA Class I Tetramers J. Immunol., December 15, 2000; 165(12): 7285 - 7292. [Abstract] [Full Text] [PDF]
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P. R. Dunbar, C. L. Smith, D. Chao, M. Salio, D. Shepherd, F. Mirza, M. Lipp, A. Lanzavecchia, F. Sallusto, A. Evans, et al. A Shift in the Phenotype of Melan-A-Specific CTL Identifies Melanoma Patients with an Active Tumor-Specific Immune Response J. Immunol., December 1, 2000; 165(11): 6644 - 6652. [Abstract] [Full Text] [PDF]
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M. K. Maini, N. Gudgeon, L. R. Wedderburn, A. B. Rickinson, and P. C. L. Beverley Clonal Expansions in Acute EBV Infection Are Detectable in the CD8 and not the CD4 Subset and Persist with a Variable CD45 Phenotype J. Immunol., November 15, 2000; 165(10): 5729 - 5737. [Abstract] [Full Text] [PDF]
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T. K. Hoffmann, K. Nakano, E. M. Elder, G. Dworacki, S. D. Finkelstein, E. Appella, T. L. Whiteside, and A. B. DeLeo Generation of T Cells Specific for the Wild-Type Sequence p53264-272 Peptide in Cancer Patients: Implications for Immunoselection of Epitope Loss Variants J. Immunol., November 15, 2000; 165(10): 5938 - 5944. [Abstract] [Full Text] [PDF]
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