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The Antiviral Efficacy of Simian Immunodeficiency Virus-Specific CD8⁺ T Cells Is Unrelated to Epitope Specificity and Is Abrogated by Viral Escape

Wisconsin National Primate Research Center,¹ Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53715,² Division of Infectious Diseases, Federal University of São Paulo, São Paulo, Brazil³

Received 1 September 2006/ Accepted 16 December 2006

CD8⁺ T lymphocytes appear to play a role in controlling human immunodeficiency virus (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 abilities of different epitope-specific CD8⁺ T-cell lines to control simian immunodeficiency virus (SIV) replication. We compared the antiviral efficacies 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 specificities 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 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 the replication of an escaped virus. Viral escape abrogated the abilities of Tat_28-35SL8- and Gag_181-189CM9-specific CD8⁺ T cells to control viral replication. However, gamma interferon (IFN-) enzyme-linked immunospot and IFN-/tumor necrosis factor alpha intracellular-cytokine-staining assays detected cross-reactive immune responses against the Gag escape variant. Understanding antiviral efficacy and epitope variability, therefore, will be important in selecting candidate epitopes for an HIV vaccine.

Published ahead of print on 27 December 2006.

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