HLA-E–restricted, Gag-specific CD8+ T cells can suppress HIV-1 infection, offering vaccine opportunities
Yang H., Rei M., Brackenridge S., Brenna E., Sun H., Abdulhaqq S., Liu MKP., Ma W., Kurupati P., Xu X., Cerundolo V., Jenkins E., Davis SJ., Sacha JB., Früh K., Picker LJ., Borrow P., Gillespie GM., McMichael AJ.
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.