小柯机器人

荷兰格罗宁根大学医学中心Alexandra Zhernakova和以色列魏茨曼科学研究所Thomas Vogl共同合作，近期取得重要工作进展。他们通过噬菌体展示测序揭示遗传、环境和内在因素影响人类抗体表位库的变异。相关研究成果2023年5月9日在线发表于《免疫》杂志上。

据介绍，噬菌体展示的免疫沉淀测序（PhIP-seq）已经实现了对人类抗体库的高通量分析。然而，对影响人类适应性免疫的环境和遗传决定因素缺乏全面的综述。在这一工作中，研究探讨了遗传、环境和内在因素对人类抗体库变异的影响。

研究人员使用PhIP-seq文库对来自1443名参与者的各种微生物和环境抗原的344000个肽血清学抗体库进行了表征。研究人员在抗体库中检测到个体特异性、时间一致性和同居相似性。遗传分析显示HLA、IGHV和FUT2基因区域参与抗体结合肽反应。

此外，研究人员发现了表型因素（包括年龄、细胞计数、性别、吸烟行为和过敏等）与特定抗体结合肽之间的关联。

总之，这一研究结果表明，人类抗体表位库是由遗传和环境暴露共同决定的，并突出了不同表型和基因型的特定特征。

附：英文原文

Title: Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire

Author: Sergio Andreu-Sánchez, Arno R. Bourgonje, Thomas Vogl, Alexander Kurilshikov, Sigal Leviatan, Angel J. Ruiz-Moreno, Shixian Hu, Trishla Sinha, Arnau Vich Vila, Shelley Klompus, Iris N. Kalka, Karina de Leeuw, Suzanne Arends, Iris Jonkers, Sebo Withoff, Elisabeth Brouwer, Adina Weinberger, Cisca Wijmenga, Eran Segal, Rinse K. Weersma, Jingyuan Fu, Alexandra Zhernakova

Issue&Volume: 2023-05-09

Abstract: Phage-displayed immunoprecipitation sequencing (PhIP-seq) has enabled high-throughputprofiling of human antibody repertoires. However, a comprehensive overview of environmentaland genetic determinants shaping human adaptive immunity is lacking. In this study,we investigated the effects of genetic, environmental, and intrinsic factors on thevariation in human antibody repertoires. We characterized serological antibody repertoiresagainst 344,000 peptides using PhIP-seq libraries from a wide range of microbial andenvironmental antigens in 1,443 participants from a population cohort. We detectedindividual-specificity, temporal consistency, and co-housing similarities in antibodyrepertoires. Genetic analyses showed the involvement of the HLA, IGHV, and FUT2 gene regions in antibody-bound peptide reactivity. Furthermore, we uncovered associationsbetween phenotypic factors (including age, cell counts, sex, smoking behavior, andallergies, among others) and particular antibody-bound peptides. Our results indicatethat human antibody epitope repertoires are shaped by both genetics and environmentalexposures and highlight specific signatures of distinct phenotypes and genotypes.

DOI: 10.1016/j.immuni.2023.04.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00171-1

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