HLA-E restricted, HIV-1 suppressing, Gag specific CD8+ T cells offer universal vaccine opportunities

Human leukocyte antigen-E (HLA-E) normally presents a 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, human immunodeficiency virus type 1 (HIV-1) specific HLA-E restricted T cells have not been observed in HIV-1-infected individuals. Here we primed HLA-E restricted HIV-1 specific CD8+ T cells 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. One Sentence Summary CD8+ T cells that recognize a Gag peptide presented by HLA-E suppress HIV-1 replication in vitro . ### Competing Interest Statement OHSU, LJP and KF have a substantial financial interest in Vir Biotechnology, Inc., a company that may have a commercial interest in the results of this research and technology. LJP and KF are also consultants to Vir Biotechnology, Inc., and JBS has received compensation for consulting for Vir Biotechnology, Inc. Oxford University has filed a patent relating to the T cell receptor sequences shown.