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

Yang, H.; Rei, M.; Brackenridge, S.; Brenna, E.; Sun, H.; abdulhaqq, s.; Liu, M. K.; Ma, W.; Kurupati, P.; Xu, x.; Cerundolo, V.; Jenkins, E.; Davis, S. J.; Sacha, J. B.; Frueh, K.; Picker, L. J.; Borrow, P.; Gillespie, G.; McMichael, A. J.

doi:10.1101/2020.12.01.406066

bioRxiv · 10.1101/2020.12.01.406066

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

Yang, H.·Rei, M.·Brackenridge, S.·Brenna, E.·Sun, H.·abdulhaqq, s.·Liu, M. K.·Ma, W.·Kurupati, P.·Xu, x.·Cerundolo, V.·Jenkins, E.·Davis, S. J.·Sacha, J. B.·Frueh, K.·Picker, L. J.·Borrow, P.·Gillespie, G.·McMichael, A. J.

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Abstract

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 SummaryCD8+ T cells that recognize a Gag peptide presented by HLA-E suppress HIV-1 replication in vitro.

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Yang, H., Rei, M., Brackenridge, S., Brenna, E., Sun, H., abdulhaqq, s., Liu, M. K., Ma, W., Kurupati, P., Xu, x., Cerundolo, V., Jenkins, E., Davis, S. J., Sacha, J. B., Frueh, K., Picker, L. J., Borrow, P., Gillespie, G., McMichael, A. J.. 2020-12-02. HLA-E restricted, HIV-1 suppressing, Gag specific CD8+ T cells offer universal vaccine opportunities. https://doi.org/10.1101/2020.12.01.406066

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