Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Immunity. 2023 Jun 13;56(6):1376-1392.e8. doi: 10.1016/j.immuni.2023.04.003. Epub 2023 May 9.
Phage-displayed immunoprecipitation sequencing (PhIP-seq) has enabled high-throughput profiling of human antibody repertoires. However, a comprehensive overview of environmental and genetic determinants shaping human adaptive immunity is lacking. In this study, we investigated the effects of genetic, environmental, and intrinsic factors on the variation in human antibody repertoires. We characterized serological antibody repertoires against 344,000 peptides using PhIP-seq libraries from a wide range of microbial and environmental antigens in 1,443 participants from a population cohort. We detected individual-specificity, temporal consistency, and co-housing similarities in antibody repertoires. Genetic analyses showed the involvement of the HLA, IGHV, and FUT2 gene regions in antibody-bound peptide reactivity. Furthermore, we uncovered associations between phenotypic factors (including age, cell counts, sex, smoking behavior, and allergies, among others) and particular antibody-bound peptides. Our results indicate that human antibody epitope repertoires are shaped by both genetics and environmental exposures and highlight specific signatures of distinct phenotypes and genotypes.
噬菌体展示免疫沉淀测序（PhIP-seq）已经实现了高通量的人类抗体库分析。然而，目前仍缺乏对塑造人类适应性免疫的环境和遗传决定因素的全面了解。在这项研究中，我们调查了遗传、环境和内在因素对人类抗体库变异的影响。我们使用 PhIP-seq 文库，对来自人群队列的 1443 名参与者的 344000 个肽进行了血清学抗体库分析，研究了针对多种微生物和环境抗原的抗体库。我们检测到了抗体库的个体特异性、时间一致性和同居住所相似性。遗传分析表明，HLA、IGHV 和 FUT2 基因区域参与了抗体结合肽的反应性。此外，我们还发现了表型因素（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。我们的研究结果表明，人类抗体表位库受遗传和环境暴露的影响，突出了不同表型和基因型的特定特征。
