Ternette Nicola, Yang Hongbing, Partridge Thomas, Llano Anuska, Cedeño Samandhy, Fischer Roman, Charles Philip D, Dudek Nadine L, Mothe Beatriz, Crespo Manuel, Fischer William M, Korber Bette T M, Nielsen Morten, Borrow Persephone, Purcell Anthony W, Brander Christian, Dorrell Lucy, Kessler Benedikt M, Hanke Tomáš
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Eur J Immunol. 2016 Jan;46(1):60-9. doi: 10.1002/eji.201545890. Epub 2015 Nov 4.
Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High-throughput definition of HLA class I-associated immunopeptidomes by mass spectrometry is an increasingly important analytical tool to advance our understanding of the induction of T-cell responses against pathogens such as HIV-1. We utilized a liquid chromatography tandem mass spectrometry workflow including de novo-assisted database searching to define the HLA class I-associated immunopeptidome of HIV-1-infected human cells. We here report for the first time the identification of 75 HIV-1-derived peptides bound to HLA class I complexes that were purified directly from HIV-1-infected human primary CD4(+) T cells and the C8166 human T-cell line. Importantly, one-third of eluted HIV-1 peptides had not been previously known to be presented by HLA class I. Over 82% of the identified sequences originated from viral protein regions for which T-cell responses have previously been reported but for which the precise HLA class I-binding sequences have not yet been defined. These results validate and expand the current knowledge of virus-specific antigenic peptide presentation during HIV-1 infection and provide novel targets for T-cell vaccine development.
细胞毒性T淋巴细胞识别并清除被感染细胞是抵御细胞内病原体的关键防御机制。通过质谱对HLA I类相关免疫肽组进行高通量定义，是增进我们对针对HIV-1等病原体的T细胞应答诱导理解的一项日益重要的分析工具。我们利用包括从头测序辅助数据库搜索的液相色谱串联质谱工作流程，来定义HIV-1感染的人类细胞的HLA I类相关免疫肽组。我们在此首次报告，从HIV-1感染的人类原代CD4(+) T细胞和C8166人类T细胞系直接纯化的与HLA I类复合物结合的75种HIV-1衍生肽的鉴定结果。重要的是，洗脱的HIV-1肽中有三分之一以前未知可由HLA I类呈递。超过82%的已鉴定序列源自先前已报道有T细胞应答但尚未确定精确HLA I类结合序列的病毒蛋白区域。这些结果验证并扩展了当前关于HIV-1感染期间病毒特异性抗原肽呈递的知识，并为T细胞疫苗开发提供了新的靶点。
