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

HLA-E 限制性、Gag 特异性 CD8+ T 细胞可抑制 HIV-1 感染,提供疫苗机会

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作者:Hongbing Yang, Margarida Rei, Simon Brackenridge, Elena Brenna, Hong Sun, Shaheed Abdulhaqq, Michael K P Liu, Weiwei Ma, Prathiba Kurupati, Xiaoning Xu, Vincenzo Cerundolo, Edward Jenkins, Simon J Davis, Jonah B Sacha, Klaus Früh, Louis J Picker, Persephone Borrow, Geraldine M Gillespie, Andrew J Mc

Abstract

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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