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Abstract：
Epstein-Barr Virus (EBV) is closely linked to nasopharyngeal carcinoma (NPC), notably prevalent in southern China. Although type II latency of EBV plays a crucial role in the development of NPC, some lytic genes and intermittent reactivation are also critical for viral propagation and tumor progression. Since T cell-mediated immunity is effective in targeted killing of EBV-positive cells, it is important to identify EBV-derived peptides presented by highly prevalent human leukocyte antigen class I (HLA-I) molecules throughout the EBV life cycle. Here, we constructed an EBV-positive NPC cell model to evaluate the presentation of EBV lytic phase peptides on streptavidin-tagged specific HLA-I molecules. Utilizing a mass spectrometry (LC-MS/MS)-based immunopeptidomic approach, we characterized eleven novel EBV peptides as well as two previously identified peptides. Furthermore, we determined these peptides were immunogenic and could stimulate PBMCs from EBV VCA/NA-IgA positive donors in an NPC endemic southern Chinese population. Overall, this work demonstrates that highly prevalent HLA-I-specific EBV peptides can be captured and functionally presented to elicit immune responses in an in vitro model, which provides insight into the epitopes presented during EBV lytic cycle and reactivation. It expands the range of viral targets for potential NPC early diagnosis and treatment.
摘要：
EB病毒（EBV）与鼻咽癌（NPC）密切相关，尤其是在中国南方。尽管EBV的II型潜伏期在NPC的发展中起着至关重要的作用，一些裂解基因和间歇性再激活对病毒繁殖和肿瘤进展也至关重要.由于T细胞介导的免疫在靶向杀伤EBV阳性细胞中是有效的,重要的是鉴定在整个EBV生命周期中由高度流行的人类白细胞抗原I类(HLA-I)分子呈递的EBV衍生肽。这里,我们构建了EBV阳性NPC细胞模型,以评估EBV裂解期肽在链霉亲和素标记的特异性HLA-I分子上的呈递。利用基于质谱（LC-MS/MS）的免疫肽方法，我们表征了11种新型EBV肽以及两种先前鉴定的肽。此外，我们确定这些肽具有免疫原性，可以刺激来自中国南方鼻咽癌地方性人群中EBVVCA/NA-IgA阳性供体的PBMC。总的来说,这项工作表明，可以捕获高度流行的HLA-I特异性EBV肽，并在体外模型中功能性呈递以引发免疫应答，这提供了对EBV裂解周期和再激活过程中呈现的表位的洞察。它扩大了潜在的NPC早期诊断和治疗的病毒靶标范围。
