Abstract：
Listeria monocytogenes is a foodborne intracellular bacterial model pathogen. Protective immunity against Listeria depends on an effective CD8+ T cell response, but very few T cell epitopes are known in mice as a common animal infection model for listeriosis. To identify epitopes, we screened for Listeria immunopeptides presented in the spleen of infected mice by mass spectrometry-based immunopeptidomics. We mapped more than 6000 mouse self-peptides presented on MHC class I molecules, including 12 high confident Listeria peptides from 12 different bacterial proteins. Bacterial immunopeptides with confirmed fragmentation spectra were further tested for their potential to activate CD8+ T cells, revealing VTYNYINI from the putative cell wall surface anchor family protein LMON_0576 as a novel bona fide peptide epitope. The epitope showed high biological potency in a prime boost model and can be used as a research tool to probe CD8+ T cell responses in the mouse models of Listeria infection. Together, our results demonstrate the power of immunopeptidomics for bacterial antigen identification.
摘要：
单核细胞增生李斯特菌是食源性细胞内细菌模型病原体。针对李斯特菌的保护性免疫取决于有效的CD8+T细胞反应，但是在小鼠中很少有T细胞表位被认为是李斯特菌病的常见动物感染模型。为了鉴定表位，我们通过基于质谱的免疫肽筛选了感染小鼠脾脏中存在的李斯特菌免疫肽。我们绘制了在MHCI类分子上呈递的6000多个小鼠自身肽，包括来自12种不同细菌蛋白的12种高度自信的李斯特菌肽。进一步测试了具有确认片段谱的细菌免疫肽激活CD8+T细胞的潜力。从推定的细胞壁表面锚家族蛋白LMON_0576中揭示VTYNYINI作为一种新型的真正的肽表位。该表位在初免加强模型中显示出高生物学效力,并且可以用作研究工具以探测李斯特菌感染的小鼠模型中的CD8+T细胞应答。一起,我们的结果证明了免疫肽用于细菌抗原鉴定的能力。
