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Viruses selectively mutate their CDB+ T-cell epitopes-a large-scale immunomic analysis

机译:病毒选择性地突变其CDB + T细胞表位 - 一种大规模的免疫分析

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Motivation: Viruses employ various means to evade immune detection. One common evasion strategy is the removal of CDB+ cytotoxic T-lymphocyte epitopes. We here use a combination of multiple bioinformatic tools and large amount of genomic data to compute the epitope repertoire presented by over 1300 viruses in many HLA alleles. We define the 'Size of Immune Repertoire score', which represents the ratio between the epitope density within a protein and the expected density. This score is used to study viral immune evasion. Results: We show that viral proteins in general have a higher epitope density than human proteins. This difference is due to a good fit of the human MHC molecules to the typical amino-acid usage of viruses. Among different viruses, viruses infecting humans present less epitopes than non-human viruses. This selection is not at the amino-acid usage level, but through the removal of specific epitopes. Within a single virus, not all proteins express the same epitopes density. Proteins expressed early in the viral life cycle have a lower epitope density than late proteins. Such a difference is not observed in non-human viruses. The removal of early epitopes and the targeting of the cellular immune response to late viral proteins, allow the virus a time interval to propagate before its host cells are destroyed by T cells.
机译:动机:病毒采用各种手段来逃避免疫检测。一种常见的逃避策略是去除CDB +细胞毒性T淋巴细胞表位。我们在这里使用多种生物信息工具和大量基因组数据的组合来计算许多HLA等位基因中超过1300个病毒的表位曲目。我们定义了“免疫力解到得分的大小”,其代表蛋白质内的表位密度与预期密度之间的比率。该分数用于研究病毒免疫逃避。结果:我们表明病毒蛋白通常具有比人蛋白质更高的表位密度。这种差异是由于人MHC分子的良好拟合到病毒的典型氨基酸使用。在不同的病毒中,感染人类的​​病毒比非人类病毒呈现较少的表位。这种选择不是在氨基酸使用水平,而是通过去除特定表位。在单一病毒内,并非所有蛋白质都表达相同的表位密度。在病毒生命周期早期表达的蛋白质具有比晚期蛋白质的表位密度较低。在非人类病毒中未观察到这种差异。去除早期表位和对晚期病毒蛋白的细胞免疫应答的靶向,允许病毒在其宿主细胞被T细胞破坏之前繁殖的时间间隔。

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