HLA-E-restricted T cells primed by a modified HLA-B*57:01 restricted HIV-1 peptide suppress HIV-1 replication

Journal article

HLA-E-restricted HIV-specific T cells offer exciting possibilities for immunotherapy. However, HLA-E binding peptides are rare. A recent study showed that in HLA-B*57:01 people living with HIV (PLWH), the peptide that dominates the T cell response, KAFSPEVIPMF (KF11), also stimulates HLA-E-restricted T cells, even though direct binding of this peptide to HLA-E could not be demonstrated. We therefore changed position 2 alanine for methionine in the peptide (referred to as KMF11) which greatly enhanced binding to HLA-E. This enabled the generation of stabilised HLA-E-KMF11 tetramers which were used to select and then grow specific T cell clones from T cells of HLA-B*57:01 negative blood donors primed with this peptide in vitro. Approximately 20% of these T cell clones reacted with HLA-E positive cells presenting the native KF11 peptide. Furthermore, these T cells inhibited replication of HIV-1 NL4-3 in CD4 T cells in vitro. Therefore, this native peptide can be presented by HLA-E to CD8 T cells, although priming in vivo may depend on cross reactivities to classical MHC Ia types. Nevertheless, such T cells could be exploitable for immunotherapy given the conservation of this HIV1 peptide epitope and the non-polymorphism in HLA-E.

Authors: Sun, H; Yang, H; Quastel, MN; Brackenridge, S; He, W

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Society for Clinical Investigation
• Journal: JCI Insight
• Pages: e203593
• Publication date: 2026-05-19
• DOI: 10.1172/jci.insight.203593
• EISSN: 2379-3708
• ISSN: 2379-3708
• Language: English
• Keywords: Cytotoxic T cell; Priming (agriculture); CD8; T cell; Epitope; In vitro; Cell; Peptide