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

Hong Sun; Hongbing Yang; Max N. Quastel; Simon Brackenridge; Wanlin He; Anna E. Kliszczak; Margarida Rei; Persephone Borrow; Geraldine M. Gillespie; Andrew J. McMichael

doi:10.1172/jci.insight.203593

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

Hong Sun,¹ Hongbing Yang,¹ Max N. Quastel,¹ Simon Brackenridge,¹ Wanlin He,¹ Anna E. Kliszczak,¹ Margarida Rei,² Persephone Borrow,¹ Geraldine M. Gillespie,¹ and Andrew J. McMichael¹

Published May 19, 2026 - More info

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Abstract

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.

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

Hong Sun,¹ Hongbing Yang,¹ Max N. Quastel,¹ Simon Brackenridge,¹ Wanlin He,¹ Anna E. Kliszczak,¹ Margarida Rei,² Persephone Borrow,¹ Geraldine M. Gillespie,¹ and Andrew J. McMichael¹

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

Hong Sun,1 Hongbing Yang,1 Max N. Quastel,1 Simon Brackenridge,1 Wanlin He,1 Anna E. Kliszczak,1 Margarida Rei,2 Persephone Borrow,1 Geraldine M. Gillespie,1 and Andrew J. McMichael1

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Hong Sun,¹ Hongbing Yang,¹ Max N. Quastel,¹ Simon Brackenridge,¹ Wanlin He,¹ Anna E. Kliszczak,¹ Margarida Rei,² Persephone Borrow,¹ Geraldine M. Gillespie,¹ and Andrew J. McMichael¹