在双胞胎和 SNP 基因分型队列中的抗体结合特异性分析表明，抗病毒抗体表位选择是一种可遗传的特征。
Analysis of antibody binding specificities in twin and SNP-genotyped cohorts reveals that antiviral antibody epitope selection is a heritable trait.
机构信息
Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
出版信息
Immunity. 2022 Jan 11;55(1):174-184.e5. doi: 10.1016/j.immuni.2021.12.004.
Human immune responses to viral infections are highly variable, but the genetic factors that contribute to this variability are not well characterized. We used VirScan, a high-throughput epitope scanning technology, to analyze pan-viral antibody reactivity profiles of twins and SNP-genotyped individuals. Using these data, we determined the heritability and genomic loci associated with antibody epitope selection, response breadth, and control of Epstein-Barr virus (EBV) viral load. 107 EBV peptide reactivities were heritable and at least two Epstein-Barr nuclear antigen 2 (EBNA-2) reactivities were associated with variants in the MHC class II locus. We identified an EBV serosignature that predicted viral load in peripheral blood mononuclear cells and was associated with variants in the MHC class I locus. Our study illustrates the utility of epitope profiling to investigate the genetics of pathogen immunity, reports heritable features of the antibody response to viruses, and identifies specific HLA loci important for EBV epitope selection.
人类对病毒感染的免疫反应具有高度变异性，但导致这种变异性的遗传因素尚未得到很好的描述。我们使用高通量表位扫描技术 VirScan 分析了双胞胎和 SNP 基因分型个体的泛病毒抗体反应谱。利用这些数据，我们确定了与抗体表位选择、反应广度和控制 EBV 病毒载量相关的遗传力和基因组位点。107 种 EBV 肽反应具有遗传性，至少两种 EBV 核抗原 2（EBNA-2）反应与 MHC Ⅱ类基因座的变异有关。我们确定了一种 EBV 血清标志物，可预测外周血单核细胞中的病毒载量，与 MHC Ⅰ类基因座的变异有关。我们的研究说明了表位分析在研究病原体免疫遗传学中的应用，报告了病毒抗体反应的遗传性特征，并确定了对 EBV 表位选择重要的特定 HLA 基因座。
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