HLA-E-restricted, Gag-specific CD8+ T cells can suppress HIV-1 infection, offering vaccine opportunities.

Human leukocyte antigen-E (HLA-E) normally presents an HLA class Ia signal peptide to the NKG2A/C-CD94 regulatory receptors on natural killer (NK) cells and T cell subsets. Rhesus macaques immunized with a cytomegalovirus-vectored simian immunodeficiency virus (SIV) vaccine generated Mamu-E (HLA-E homolog)–restricted T cell responses that mediated post-challenge SIV replication arrest in >50% of animals. However, HIV-1–specific, HLA-E–restricted T cells have not been observed in HIV-1–infected individuals. Here, HLA-E–restricted, HIV-1–specific CD8+ T cells were primed in vitro. These T cell clones and allogeneic CD8+ T cells transduced with their T cell receptors suppressed HIV-1 replication in CD4+ T cells in vitro. Vaccine induction of efficacious HLA-E–restricted HIV-1–specific T cells should therefore be possible.