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Viral peptide is key to T cell priming Simian immunodeficiency virus (SIV) vaccines containing a strain 68-1 rhesus cytomegalovirus (RhCMV) vector elicit strong CD8+ T cell responses that can control and clear SIV infections. The SIV peptides targeted by these T cells are presented on major histocompatibility complex (MHC) II and the nonclassical MHC-Ib molecule MHC-E rather than the more typical MHC-Ia. Verweijet al. show that the 68-1 RhCMV–encoded peptide VL9 drives intracellular transport of MHC-E and recognition of RhCMV-infected targets by MHC-E–restricted CD8+ T cells. Rhesus macaques vaccinated with a mutant 68-1 RhCMV lacking VL9 showed no priming of MHC-E–restricted CD8+ T cells and no protection against SIV. This work strongly suggests that future effective CMV-based HIV vaccines in humans will also require MHC-E–restricted CD8+ T cell priming.Science , this issue p.eabe9233

Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy