We report detailed peptide‐binding affinities between 438 HLA Class I and Class II proteins and complete proteomes of seven pandemic human viruses, including coronaviruses, influenza viruses and HIV‐1. We contrast these affinities with HLA allele frequencies across hundreds of human populations worldwide. Statistical modelling shows that peptide‐binding affinities classified into four distinct categories depend on the HLA locus but that the type of virus is only a weak predictor, except in the case of HIV‐1. Among the strong HLA binders (IC₅₀ ≤ 50), we uncovered 16 alleles (the top ones being A*02:02, B*15:03 and DRB1*01:02) binding more than 1% of peptides derived from all viruses, 9 (top ones including HLA‐A*68:01, B*15:25, C*03:02 and DRB1*07:01) binding all viruses except HIV‐1, and 15 (top ones A*02:01 and C*14:02) only binding coronaviruses. The frequencies of strongest and weakest HLA peptide binders differ significantly among populations from different geographic regions. In particular, Indigenous peoples of America show both higher frequencies of strongest and lower frequencies of weakest HLA binders. As many HLA proteins are found to be strong binders of peptides derived from distinct viral families, and are hence promiscuous (or generalist), we discuss this result in relation to possible signatures of natural selection on HLA promiscuous alleles due to past pathogenic infections. Our findings are highly relevant for both evolutionary genetics and the development of vaccine therapies. However they should not lead to forget that individual resistance and vulnerability to diseases go beyond the sole HLA allelic affinity and depend on multiple, complex and often unknown biological, environmental and other variables.

中文翻译：

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438 种 HLA 蛋白与七种大流行病毒的完整蛋白质组的结合亲和力以及全球人群中最强和最弱 HLA 肽结合剂的分布。

我们报告了 438 种 HLA I 类和 II 类蛋白质与七种大流行人类病毒（包括冠状病毒、流感病毒和 HIV-1）的完整蛋白质组之间的详细肽结合亲和力。我们将这些亲和力与全球数百个人群的 HLA 等位基因频率进行对比。统计模型表明，分为四个不同类别的肽结合亲和力取决于 HLA 基因座，但病毒类型只是一个弱预测因子，除了 HIV-1 的情况。在强 HLA 结合剂 (IC ₅₀ ≤ 50) 中，我们发现了 16 个等位基因（最重要的是A*02:02、B*15:03和DRB1*01:02）结合超过 1% 的所有病毒肽, 9（包括HLA-A*68:01在内的顶级, B*15:25 , C*03:02和DRB1*07:01 ) 结合除 HIV-1 和 15 之外的所有病毒（最上面的A*02:01和C*14:02) 仅结合冠状病毒。来自不同地理区域的人群中最强和最弱的 HLA 肽结合剂的频率存在显着差异。特别是，美洲原住民表现出较高频率的最强 HLA 结合剂和较低频率的最弱 HLA 结合剂。由于发现许多 HLA 蛋白是来自不同病毒家族的肽的强结合剂，因此是混杂的（或通才的），我们讨论了这一结果与由于过去的病原体感染导致的 HLA 混杂等位基因的自然选择的可能特征有关。我们的研究结果与进化遗传学和疫苗疗法的开发高度相关。然而，它们不应导致忘记个体对疾病的抵抗力和易感性超出了唯一的 HLA 等位基因亲和力并依赖于多种，