The antiviral efficacy of simian immunodeficiency virus-specific CD8 ⁺ T cells is unrelated to epitope specificity and is abrogated by viral escape

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-γ) enzyme-linked immunospot and IFN-γ/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.