Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.
Viruses. 2022 May 11;14(5):1019. doi: 10.3390/v14051019.
HLA-B57:01 is an HLA allelic variant associated with positive outcomes during viral infections through interactions with T cells and NK cells, but severe disease in persons treated with the anti-HIV-1 drug abacavir. The role of HLA-B57:01 in the context of HSV infection is unknown. We identified an HLA-B57:01-restricted CD8 T-cell epitope in the ICP22 (US1) protein of HSV-2. CD8 T cells reactive to the HSV-2 ICP22 epitope recognized the orthologous HSV-1 peptide, but not closely related peptides in human IFNL2 or IFNL3. Abacavir did not alter the CD8 T-cell recognition of the HSV or self-derived peptides. Unexpectedly, a tetramer of HSV-2 ICP22 epitope (228-236) and HLA-B57:01 bound both CD8 T cells and NK cells. Tetramer specificity for KIR3DL1 was confirmed using KIR3DL1 overexpression on non-human primate cells lacking human KIR and studies with blocking anti-KIR3DL1 antibody. Interaction with KIR3DL1 was generalizable to donors lacking the genotype or HSV seropositivity. These findings suggest a mechanism for the recognition of HSV infection by NK cells or KIR-expressing T cells via KIR3DL1.
HLA-B57:01 是一种与病毒感染期间的 T 细胞和 NK 细胞相互作用相关的 HLA 等位基因变体，与接受抗 HIV-1 药物阿巴卡韦治疗的患者的严重疾病有关。HLA-B57:01 在单纯疱疹病毒感染中的作用尚不清楚。我们在单纯疱疹病毒 2（HSV-2）的 ICP22（US1）蛋白中鉴定出一个 HLA-B57:01 限制性 CD8 T 细胞表位。对 HSV-2 ICP22 表位有反应的 CD8 T 细胞识别与 HSV-1 同源的肽，但不能识别人类 IFNL2 或 IFNL3 中的密切相关肽。阿巴卡韦不会改变 CD8 T 细胞对单纯疱疹病毒或自身衍生肽的识别。出乎意料的是，HSV-2 ICP22 表位（228-236）和 HLA-B57:01 的四聚体结合了 CD8 T 细胞和 NK 细胞。使用缺乏人类 KIR 的非人类灵长类细胞上表达的 KIR3DL1 证实了四聚体对 KIR3DL1 的特异性，并使用阻断抗 KIR3DL1 抗体进行了研究。与 KIR3DL1 的相互作用可推广到缺乏 基因型或 HSV 血清阳性的供体。这些发现表明了 NK 细胞或 KIR 表达 T 细胞通过 KIR3DL1 识别单纯疱疹病毒感染的机制。
