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

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; Lifelines Cohort Study; Elisabeth Brouwer; Adina Weinberger; Cisca Wijmenga; Eran Segal; Rinse K Weersma; Jingyuan Fu; Alexandra Zhernakova

doi:10.1016/j.immuni.2023.04.003

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

Immunity. 2023 Jun 13;56(6):1376-1392.e8. doi: 10.1016/j.immuni.2023.04.003. Epub 2023 May 9.

Authors

Sergio Andreu-Sánchez¹, Arno R Bourgonje², Thomas Vogl³, Alexander Kurilshikov⁴, Sigal Leviatan⁵, Angel J Ruiz-Moreno⁴, Shixian Hu⁶, Trishla Sinha⁴, Arnau Vich Vila⁶, Shelley Klompus⁵, Iris N Kalka⁷, Karina de Leeuw⁸, Suzanne Arends⁸, Iris Jonkers⁴, Sebo Withoff⁴; Lifelines Cohort Study⁴; Elisabeth Brouwer⁸, Adina Weinberger⁵, Cisca Wijmenga⁴, Eran Segal⁵, Rinse K Weersma², Jingyuan Fu¹, Alexandra Zhernakova⁹

Affiliations

¹ 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.
² Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University Graz, Graz, Austria; Center for Cancer Research, Medical University of Vienna, Wien, Austria. Electronic address: thomas.vogl@meduniwien.ac.at.
⁴ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁵ Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
⁶ Department of Genetics, 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.
⁷ Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
⁸ Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁹ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: sashazhernakova@gmail.com.

PMID: 37164013
DOI: 10.1016/j.immuni.2023.04.003

Abstract

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.

Keywords: PhIP-seq; antibody repertoire; environment; genetics; lifestyle.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies*
Antigens
Bacteriophages*
Epitopes / genetics
Humans
Peptides

Substances

Antibodies
Antigens
Epitopes
Peptides