Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia;
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):3112-3117. doi: 10.1073/pnas.1815239116. Epub 2019 Feb 4.
CD8 T cells are essential effectors in antiviral immunity, recognizing 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 more than 170 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 in at least one infected mouse, and nearly 40% were immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the distribution of responses across mice give us insight into the specificity of antiviral CD8 T cell responses.
CD8 T 细胞是抗病毒免疫的关键效应器，它们能够识别由 MHC Ⅰ类分子（pMHCI）呈递的源自病毒的短肽，这些短肽存在于受感染细胞的表面。然而，对于任何病毒而言，尚未证明感染细胞上存在能够引发免疫反应的病毒 pMHCI 片段。为了研究这个基本问题，我们使用高分辨率质谱法进行肽测序，以鉴定超过 170 种在感染的小鼠细胞上呈现的痘苗病毒 pMHCI。接下来，我们在多种病毒感染的小鼠中筛选每个肽的免疫原性，揭示了广泛的免疫原性。令人惊讶的是，至少有一种感染小鼠中的 pMHCI 具有高比例（>80%）的免疫原性，近 40%的 pMHCI 在超过一半的筛选小鼠中具有免疫原性。发现如此多的肽具有免疫原性，以及反应在小鼠中的分布，使我们能够深入了解抗病毒 CD8 T 细胞反应的特异性。
