Pol-Specific CD8 + T Cells Recognize Simian Immunodeficiency Virus-Infected Cells Prior to Nef-Mediated Major Histocompatibility Complex Class I Downregulation

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Abstract
Effective, vaccine-induced CD8 + T-cell responses should recognize infected cells early enough to prevent production of progeny virions. We have recently shown that Gag-specific CD8 + T cells recognize simian immunodeficiency virus-infected cells at 2 h postinfection, whereas Env-specific CD8 + T cells do not recognize infected cells until much later in infection. However, it remains unknown when other proteins present in the viral particle are presented to CD8 + T cells after infection. To address this issue, we explored CD8 + T-cell recognition of epitopes derived from two other relatively large virion proteins, Pol and Nef. Surprisingly, infected cells efficiently presented CD8 + T-cell epitopes from virion-derived Pol proteins within 2 h of infection. In contrast, Nef-specific CD8 + T cells did not recognize infected cells until 12 h postinfection. Additionally, we show that SIVmac239 Nef downregulated surface major histocompatibility complex class I (MHC-I) molecules beginning at 12 h postinfection, concomitant with presentation of Nef-derived CD8 + T-cell epitopes. Finally, Pol-specific CD8 + T cells eliminated infected cells as early as 6 h postinfection, well before MHC-I downregulation, suggesting a previously underappreciated antiviral role for Pol-specific CD8 + T cells.

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