HLA-E 限制的、Gag 特异性的 CD8 T 细胞可以抑制 HIV-1 感染，为疫苗提供了机会。
HLA-E-restricted, Gag-specific CD8 T cells can suppress HIV-1 infection, offering vaccine opportunities.
机构信息
NDM Research Building, Nuffield Department of Medicine, Oxford University, Oxford OX3 7FZ, UK.
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, UK.
出版信息
Sci Immunol. 2021 Mar 25;6(57). doi: 10.1126/sciimmunol.abg1703.
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.
摘要
人类白细胞抗原-E（HLA-E）通常向自然杀伤（NK）细胞和 T 细胞亚群上的 NKG2A/C-CD94 调节受体呈现 HLA 类 I 信号肽。用巨细胞病毒载体的猴免疫缺陷病毒（SIV）疫苗免疫恒河猴，产生了 Mamu-E（HLA-E 同源物）限制性 T 细胞反应，在 >50%的动物中介导了 SIV 复制后的阻断。然而，在 HIV-1 感染个体中尚未观察到 HIV-1 特异性 HLA-E 限制性 T 细胞。在此，体外诱导了 HLA-E 限制性 HIV-1 特异性 CD8+T 细胞。这些 T 细胞克隆和转导了其 T 细胞受体的同种异体 CD8+T 细胞在体外抑制了 CD4+T 细胞中的 HIV-1 复制。因此，应该有可能诱导有效的 HLA-E 限制性 HIV-1 特异性 T 细胞疫苗。
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