Research ArticleHIV

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

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Science Immunology  25 Mar 2021:
Vol. 6, Issue 57, eabg1703
DOI: 10.1126/sciimmunol.abg1703

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Making human T cells see HIV-1

Cytomegalovirus (CMV)–based vaccines protect rhesus macaques from simian immunodeficiency virus infection by inducing atypical CD8+ T cell responses restricted to the rhesus HLA-E homolog. However, it is unclear whether these atypical CD8+ T cell responses might translate to human immunodeficiency virus (HIV) when using a vaccine based on a human CMV vector. Here, Yang et al. showed that HIV-1 Gag-specific, HLA-E–restricted CD8+ T cell clones could be generated in vitro from naïve T cells taken from HIV-1 uninfected people. These CD8+ T cell clones were able to suppress HIV-1–infected CD4+ target cells. These data indicate that HIV-1–specific, HLA-E–restricted CD8+ T cell clones can be generated in humans and that a human CMV vector–based vaccine for HIV may generate protective CD8+ T cell responses.


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.

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