Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1311K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pudney, V. A. Articles by Hislop, A. D. Search for Related Content PubMed PubMed Citation Articles by Pudney, V. A. Articles by Hislop, A. D. Social Bookmarking                            What's this?

Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

CORRESPONDENCE A.B. Rickinson: A.B.Rickinson{at}bham.ac.uk

Antigen immunodominance is an unexplained feature of CD8⁺ T cell responses to herpesviruses, which are agents whose lytic replication involves the sequential expression of immediate early (IE), early (E), and late (L) proteins. Here, we analyze the primary CD8 response to Epstein-Barr virus (EBV) infection for reactivity to 2 IE proteins, 11 representative E proteins, and 10 representative L proteins, across a range of HLA backgrounds. Responses were consistently skewed toward epitopes in IE and a subset of E proteins, with only occasional responses to novel epitopes in L proteins. CD8⁺ T cell clones to representative IE, E, and L epitopes were assayed against EBV-transformed lymphoblastoid cell lines (LCLs) containing lytically infected cells. This showed direct recognition of lytically infected cells by all three sets of effectors but at markedly different levels, in the order IE > E >> L, indicating that the efficiency of epitope presentation falls dramatically with progress of the lytic cycle. Thus, EBV lytic cycle antigens display a hierarchy of immunodominance that directly reflects the efficiency of their presentation in lytically infected cells; the CD8⁺ T cell response thereby focuses on targets whose recognition leads to maximal biologic effect.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Hasan, A. N., Kollen, W. J., Trivedi, D., Selvakumar, A., Dupont, B., Sadelain, M., O'Reilly, R. J. (2009). A Panel of Artificial APCs Expressing Prevalent HLA Alleles Permits Generation of Cytotoxic T Cells Specific for Both Dominant and Subdominant Viral Epitopes for Adoptive Therapy. J. Immunol. 183: 2837-2850 [Abstract] [Full Text]  
• Long, H. M., Zuo, J., Leese, A. M., Gudgeon, N. H., Jia, H., Taylor, G. S., Rickinson, A. B. (2009). CD4+ T-cell clones recognizing human lymphoma-associated antigens: generation by in vitro stimulation with autologous Epstein-Barr virus-transformed B cells. Blood 114: 807-815 [Abstract] [Full Text]  
• Pender, M P, Csurhes, P A, Lenarczyk, A, Pfluger, C M M, Burrows, S R (2009). Decreased T cell reactivity to Epstein-Barr virus infected lymphoblastoid cell lines in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 80: 498-505 [Abstract] [Full Text]  
• Bell, M. J., Abbott, R. J. M., Croft, N. P., Hislop, A. D., Burrows, S. R. (2009). An HLA-A2-Restricted T-Cell Epitope Mapped to the BNLF2a Immune Evasion Protein of Epstein-Barr Virus That Inhibits TAP. J. Virol. 83: 2783-2788 [Abstract] [Full Text]  
• Goodyear, O. C., Pratt, G., McLarnon, A., Cook, M., Piper, K., Moss, P. (2008). Differential pattern of CD4+ and CD8+ T-cell immunity to MAGE-A1/A2/A3 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Blood 112: 3362-3372 [Abstract] [Full Text]  
• Verweij, M. C., Koppers-Lalic, D., Loch, S., Klauschies, F., de la Salle, H., Quinten, E., Lehner, P. J., Mulder, A., Knittler, M. R., Tampe, R., Koch, J., Ressing, M. E., Wiertz, E. J. H. J. (2008). The Varicellovirus UL49.5 Protein Blocks the Transporter Associated with Antigen Processing (TAP) by Inhibiting Essential Conformational Transitions in the 6+6 Transmembrane TAP Core Complex. J. Immunol. 181: 4894-4907 [Abstract] [Full Text]  
• Oseroff, C., Peters, B., Pasquetto, V., Moutaftsi, M., Sidney, J., Panchanathan, V., Tscharke, D. C., Maillere, B., Grey, H., Sette, A. (2008). Dissociation between Epitope Hierarchy and Immunoprevalence in CD8 Responses to Vaccinia Virus Western Reserve. J. Immunol. 180: 7193-7202 [Abstract] [Full Text]  
• Adhikary, D., Behrends, U., Feederle, R., Delecluse, H.-J., Mautner, J. (2008). Standardized and Highly Efficient Expansion of Epstein-Barr Virus-Specific CD4+ T Cells by Using Virus-Like Particles. J. Virol. 82: 3903-3911 [Abstract] [Full Text]  
• Zuo, J., Thomas, W., van Leeuwen, D., Middeldorp, J. M., Wiertz, E. J. H. J., Ressing, M. E., Rowe, M. (2008). The DNase of Gammaherpesviruses Impairs Recognition by Virus-Specific CD8+ T Cells through an Additional Host Shutoff Function. J. Virol. 82: 2385-2393 [Abstract] [Full Text]  
• Vider-Shalit, T., Fishbain, V., Raffaeli, S., Louzoun, Y. (2007). Phase-Dependent Immune Evasion of Herpesviruses. J. Virol. 81: 9536-9545 [Abstract] [Full Text]  
• Hislop, A. D., Ressing, M. E., van Leeuwen, D., Pudney, V. A., Horst, D., Koppers-Lalic, D., Croft, N. P., Neefjes, J. J., Rickinson, A. B., Wiertz, E. J.H.J. (2007). A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates. JEM 204: 1863-1873 [Abstract] [Full Text]  
• Bihl, F., Narayan, M., Chisholm, J. V. III, Henry, L. M., Suscovich, T. J., Brown, E. E., Welzel, T. M., Kaufmann, D. E., Zaman, T. M., Dollard, S., Martin, J. N., Wang, F., Scadden, D. T., Kaye, K. M., Brander, C. (2007). Lytic and Latent Antigens of the Human Gammaherpesviruses Kaposi's Sarcoma-Associated Herpesvirus and Epstein-Barr Virus Induce T-Cell Responses with Similar Functional Properties and Memory Phenotypes. J. Virol. 81: 4904-4908 [Abstract] [Full Text]  
• Guerreiro-Cacais, A. O., Uzunel, M., Levitskaya, J., Levitsky, V. (2007). Inhibition of Heavy Chain and {beta}2-Microglobulin Synthesis as a Mechanism of Major Histocompatibility Complex Class I Downregulation during Epstein-Barr Virus Replication. J. Virol. 81: 1390-1400 [Abstract] [Full Text]  
• Pappworth, I. Y., Wang, E. C., Rowe, M. (2007). The Switch from Latent to Productive Infection in Epstein-Barr Virus-Infected B Cells Is Associated with Sensitization to NK Cell Killing. J. Virol. 81: 474-482 [Abstract] [Full Text]  
• Taylor, G. S., Long, H. M., Haigh, T. A., Larsen, M., Brooks, J., Rickinson, A. B. (2006). A Role for Intercellular Antigen Transfer in the Recognition of EBV-Transformed B Cell Lines by EBV Nuclear Antigen-Specific CD4+ T Cells. J. Immunol. 177: 3746-3756 [Abstract] [Full Text]  
• Feng, W.-h., Kenney, S. C. (2006). Valproic Acid Enhances the Efficacy of Chemotherapy in EBV-Positive Tumors by Increasing Lytic Viral Gene Expression.. Cancer Res. 66: 8762-8769 [Abstract] [Full Text]  
• Sauce, D., Larsen, M., Curnow, S. J., Leese, A. M., Moss, P. A. H., Hislop, A. D., Salmon, M., Rickinson, A. B. (2006). EBV-associated mononucleosis leads to long-term global deficit in T-cell responsiveness to IL-15. Blood 108: 11-18 [Abstract] [Full Text]  
• Boon, A. C. M., de Mutsert, G., Fouchier, R. A. M., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2006). The Hypervariable Immunodominant NP418-426 Epitope from the Influenza A Virus Nucleoprotein Is Recognized by Cytotoxic T Lymphocytes with High Functional Avidity.. J. Virol. 80: 6024-6032 [Abstract] [Full Text]  
• Fogg, M. H., Garry, D., Awad, A., Wang, F., Kaur, A. (2006). The BZLF1 Homolog of an Epstein-Barr-Related {gamma}-Herpesvirus Is a Frequent Target of the CTL Response in Persistently Infected Rhesus Macaques. J. Immunol. 176: 3391-3401 [Abstract] [Full Text]  
• Yuan, J., Cahir-McFarland, E., Zhao, B., Kieff, E. (2006). Virus and Cell RNAs Expressed during Epstein-Barr Virus Replication. J. Virol. 80: 2548-2565 [Abstract] [Full Text]  
• Landais, E., Saulquin, X., Bonneville, M., Houssaint, E. (2005). Long-Term MHC Class II Presentation of the EBV Lytic Protein BHRF1 by EBV Latently Infected B Cells following Capture of BHRF1 Antigen. J. Immunol. 175: 7939-7946 [Abstract] [Full Text]  
• Tynan, F. E., Elhassen, D., Purcell, A. W., Burrows, J. M., Borg, N. A., Miles, J. J., Williamson, N. A., Green, K. J., Tellam, J., Kjer-Nielsen, L., McCluskey, J., Rossjohn, J., Burrows, S. R. (2005). The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation. JEM 202: 1249-1260 [Abstract] [Full Text]  
• Tebo, A. E., Fuller, M. J., Gaddis, D. E., Kojima, K., Rehani, K., Zajac, A. J. (2005). Rapid Recruitment of Virus-Specific CD8 T Cells Restructures Immunodominance during Protective Secondary Responses. J. Virol. 79: 12703-12713 [Abstract] [Full Text]  
• Ressing, M. E., Keating, S. E., van Leeuwen, D., Koppers-Lalic, D., Pappworth, I. Y., Wiertz, E. J. H. J., Rowe, M. (2005). Impaired Transporter Associated with Antigen Processing-Dependent Peptide Transport during Productive EBV Infection. J. Immunol. 174: 6829-6838 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS