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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3414-3419. Prepublished online as a Blood First Edition Paper on August 1, 2006; DOI 10.1182/blood-2006-06-030668. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-06-030668v1 108/10/3414    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Adnan, S. Articles by Yang, O. O. Search for Related Content PubMed PubMed Citation Articles by Adnan, S. Articles by Yang, O. O. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Nef interference with HIV-1–specific CTL antiviral activity is epitope specific Sama Adnan, Arumugam Balamurugan, Alicja Trocha, Michael S. Bennett, Hwee L. Ng, Ayub Ali, Christian Brander, and Otto O. Yang From the Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles; Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles; and Partners AIDS Research Center, Massachusetts General Hospital, Harvard University, Boston. HIV-1 Nef and HIV-1–specific cytotoxic T lymphocytes (CTLs) have important and opposing roles in the immunopathogenesis of HIV-1 infection. Nef-mediated down-modulation of HLA class I on infected cells can confer resistance to CTL clearance, but the factors determining the efficiency of this process are unknown. This study examines the impact of Nef on the antiviral activity of several CTL clones recognizing epitopes from early and late HIV-1 proteins, restricted by HLA-A, -B, and -C molecules. CTL-targeting epitopes in early proteins remained susceptible to the effects of Nef, although possibly to a lesser degree than CTL-targeting late protein epitopes, indicating that significant Nef-mediated HLA down-regulation can precede even the presentation of early protein-derived epitopes. However, HLA-C–restricted CTLs were unaffected by Nef, consistent with down-regulation of cell-surface HLA-A and -B but not HLA-C molecules. Thus, CTLs vary dramatically in their susceptibility to Nef interference, suggesting differences in the relative importance of HLA-A– and HLA-B– versus HLA-C–restricted CTLs in vivo. The data thus indicate that HLA-C–restricted CTLs may have an under-appreciated antiviral role in the setting of Nef in vivo and suggest a benefit of promoting HLA-C–restricted CTLs for immunotherapy or vaccine development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. M. Rousseau, M. G. Daniels, J. M. Carlson, C. Kadie, H. Crawford, A. Prendergast, P. Matthews, R. Payne, M. Rolland, D. N. Raugi, et al. HLA Class I-Driven Evolution of Human Immunodeficiency Virus Type 1 Subtype C Proteome: Immune Escape and Viral Load J. Virol., July 1, 2008; 82(13): 6434 - 6446. [Abstract] [Full Text] [PDF] J. B. Sacha, C. Chung, J. Reed, A. K. Jonas, A. T. Bean, S. P. Spencer, W. Lee, L. Vojnov, R. Rudersdorf, T. C. Friedrich, et al. Pol-Specific CD8+ T Cells Recognize Simian Immunodeficiency Virus-Infected Cells Prior to Nef-Mediated Major Histocompatibility Complex Class I Downregulation J. Virol., November 1, 2007; 81(21): 11703 - 11712. [Abstract] [Full Text] [PDF] B. Poon, M. A. Chang, and I. S. Y. Chen Vpr Is Required for Efficient Nef Expression from Unintegrated Human Immunodeficiency Virus Type 1 DNA J. Virol., October 1, 2007; 81(19): 10515 - 10523. [Abstract] [Full Text] [PDF] J. Fellay, K. V. Shianna, D. Ge, S. Colombo, B. Ledergerber, M. Weale, K. Zhang, C. Gumbs, A. Castagna, A. Cossarizza, et al. A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1 Science, August 17, 2007; 317(5840): 944 - 947. [Abstract] [Full Text] [PDF]

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