The majority of viral peptides displayed on class I MHC are immunogenic during infection

CD8+ T cells are essential effectors in anti-viral immunity, recognising short virus-derived peptides presented by MHC class I (pMHCI) on the surface of infected cells. However, the fraction of viral pMHCI on infected cells that are immunogenic has not been shown for any virus. To approach this fundamental question, we used peptide sequencing by high-resolution mass spectrometry to identify nearly 200 vaccinia virus pMHCI presented on infected mouse cells. Next, we screened each peptide for immunogenicity in multiple virus-infected mice, revealing a wide range of immunogenicities. A surprisingly high fraction (>80%) of pMHCI were immunogenic at least one infected animal and around half of these were dominant, which we define as being immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the variability in immunogenicity across mice give us new insight into the specificity of anti-viral CD8+ T cell responses.

CD8+ T细胞（CD8+ T cells）是抗病毒免疫中的核心效应细胞，可识别受感染细胞表面由主要组织相容性复合体I类（MHC class I，pMHCI）呈递的病毒来源短肽。然而，目前尚无任何病毒被证实，其受感染细胞表面的病毒源性pMHCI中具备免疫原性的具体占比。为解答这一基础科学问题，本研究采用高分辨率质谱技术开展肽段测序，在受感染的小鼠细胞中鉴定出近200种痘苗病毒（vaccinia virus）来源的pMHCI。随后，我们在多只病毒感染的小鼠体内对每一种肽段的免疫原性进行筛选检测，结果显示免疫原性水平存在广泛差异。令人意外的是，高达80%以上的pMHCI在至少一只受感染小鼠体内呈现免疫原性；其中约半数属于优势免疫原性肽段，本研究将其定义为在超过半数受筛选小鼠体内均能诱发免疫应答的肽段。本次研究鉴定出大量具有免疫原性的肽段，且不同小鼠间的免疫原性存在显著差异，这为阐明抗病毒CD8+ T细胞应答的特异性提供了全新视角。