Phage display of environmental protein toxins and virulence factors reveals the prevalence, persistence, and genetics of antibody responses.
Phage display of environmental protein toxins and virulence factors reveals the prevalence, persistence, and genetics of antibody responses.
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DOI：
10.1016/j.immuni.2022.05.002
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发表时间：
2022-06-14
期刊：
影响因子：
32.4
通讯作者：
Larman, H. Benjamin
中科院分区：
文献类型：
--
作者：
Angkeow, Julia W.;Monaco, Daniel R.;Chen, Athena;Venkataraman, Thiagarajan;Jayaraman, Sahana;Valencia, Cristian;Sie, Brandon M.;Liechti, Thomas;Farhadi, Payam N.;Funez-dePagnier, Gabriela;Sherman-Baust, Cheryl A.;Wong, May Q.;Ruczinski, Ingo;Caturegli, Patrizio;Sears, Cynthia L.;Simner, Patricia J.;Round, June L.;Duggal, Priya;Laserson, Uri;Steiner, Theodore S.;Sen, Ranjan;Lloyd, Thomas E.;Roederer, Mario;Mammen, Andrew L.;Longman, Randy S.;Rider, Lisa G.;Larman, H. Benjamin
微生物暴露是通过塑造免疫系统和微生物群影响健康寿命的关键环境因素。通过噬菌体免疫沉淀测序（PhIP-Seq）进行抗体谱分析，为检测微生物蛋白产品的暴露和反应提供了一种高通量、具有成本效益的方法。我们设计并构建了一个包含95，601个56-氨基酸肽片的文库，涵盖了14，430个带有“毒素”或“毒力因子”关键词注释的蛋白质。我们使用PhIP-Seq分析了约1，000个个体针对该“ToxScan”文库的抗体。除了列举广泛存在的抗体表位，我们研究了ToxScan谱的年龄依赖性稳定性，并使用全基因组关联研究发现MHC-II位点调节细菌表位选择。我们检测了先前描述的抗鞭毛蛋白抗体反应在克罗恩病队列，并确定了抗鞭毛蛋白抗体和青少年皮肌炎之间的关联。因此，PhIP-Seq与ToxScan库是在队列规模上研究健康和疾病的环境决定因素的有效工具。终生接触微生物及其蛋白质产品会对人类健康产生深远影响。Angkeow等人进行了泛毒素、泛毒力因子PhIP-Seq，用于健康志愿者和自身炎性疾病患者的抗体谱分析。他们报告说，肽结合库在成年期是独特和稳定的，并受到MHC-II基因座的调节。克罗恩病相关鞭毛蛋白抗体在青少年皮肌炎患者中发现。
Microbial exposures are crucial environmental factors that impact healthspan by sculpting the immune system and microbiota. Antibody profiling via Phage ImmunoPrecipitation Sequencing (PhIP-Seq) provides a high-throughput, cost-effective approach for detecting exposure and response to microbial protein products. We designed and constructed a library of 95,601 56-amino acid peptide tiles spanning 14,430 proteins with “toxin” or “virulence factor” keyword annotations. We used PhIP-Seq to profile the antibodies of ~1,000 individuals against this “ToxScan” library. In addition to enumerating broadly pervasive antibody epitopes, we studied the age-dependent stability of the ToxScan profile and used a genome-wide association study to find that the MHC-II locus modulates bacterial epitope selection. We detected previously described anti-flagellin antibody responses in a Crohn’s disease cohort and identified an association between anti-flagellin antibodies and juvenile dermatomyositis. PhIP-Seq with the ToxScan library is thus an effective tool for studying environmental determinants of health and disease at cohort scale. Lifelong exposures to microbes and their protein products profoundly impact human health. Angkeow et al. performed pan-toxin, pan-virulence factor PhIP-Seq for antibody profiling of healthy volunteers and patients with autoinflammatory diseases. They report that peptide binding repertoires are unique and stable in adulthood, and are modulated by the MHC-II locus. Crohn’s disease-associated flagellin antibodies are found in juvenile dermatomyositis patients.
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