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–positive people with HIV, 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 stabilized 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 HIV-1 peptide epitope and the non-polymorphism in HLA-E.
Authors
Hong Sun, Hongbing Yang, Max N. Quastel, Simon Brackenridge, Wanlin He, Anna E. Kliszczak, Margarida Rei, Persephone Borrow, Geraldine M. Gillespie, Andrew J. McMichael
Figure 2
Generation of KMF11-specific HLA-E–restricted CD8 cell clones using an in vitro DC-differentiated T cell–priming assay.
