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J. Virol. doi:10.1128/JVI.01912-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

SIV-specific CD8⁺ T cell antiviral efficacy is unrelated to epitope specificity and abrogated by viral escape

Wisconsin National Primate Research Center (WNPRC) and Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53715. Division of Infectious Diseases, Federal University of São Paulo, São Paulo-Brazil

^* To whom correspondence should be addressed. Email: watkins{at}primate.wisc.edu.

	Abstract

CD8⁺ T lymphocytes appear to play a role in controlling HIV replication, yet routine immunological assays do not measure the antiviral efficacy of these cells. Furthermore, it has been suggested that CD8⁺ T cells that recognize epitopes derived from proteins expressed early in the viral replication cycle can be highly efficient. We used a functional in vitro assay to assess the ability of different epitope-specific CD8⁺ T cell lines to control simian immunodeficiency virus (SIV) replication. We compared the antiviral efficacy of 26 epitope-specific CD8⁺ T cell lines directed against seven SIV epitopes in Tat, Nef, Gag, Env, and Vif that were restricted by either Mamu-A*01 or Mamu-A*02. Suppression of SIV replication varied depending on the epitope specificity of the CD8⁺ T cells and was unrelated to whether the targeted epitope was derived from an early or late viral protein. Tat_28-35SL8- and Gag_181-189CM9-specific CD8⁺ T cell lines were consistently superior at suppressing viral replication when compared to the other five SIV-specific CD8⁺ T cell lines. We also investigated the impact of viral escape on antiviral efficacy by determining if Tat_28-35SL8- and Gag_181-189CM9-specific CD8⁺ T cell lines could suppress replication of an escaped virus. Viral escape abrogated the ability of Tat_28-35SL8- and Gag_181-189CM9-specific CD8⁺ T cells to control viral replication. However, IFN- ELISPOT and IFN-/TNF- ICS assays detected cross-reactive immune responses against the Gag escape variant. Understanding antiviral efficacy and epitope variability will, therefore, be important in selecting candidate epitopes for an HIV vaccine.

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