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

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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.

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Author and article information

Journal

Journal ID (iso-abbrev): Immunity

Title: Immunity

Publisher: Elsevier BV

ISSN (Electronic): 1097-4180

ISSN (Print): 1074-7613

Publication date (Electronic): Jun 13 2023

Volume: 56

Issue: 6

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.

Article

Publisher Item ID: S1074-7613(23)00171-1

DOI: 10.1016/j.immuni.2023.04.003

PubMed ID: 37164013

SO-VID: 3aaeea06-b961-4150-92fd-42e9f42b592a

History

Keywords: environment,PhIP-seq,antibody repertoire,genetics,lifestyle

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Keywords: environment, PhIP-seq, antibody repertoire, genetics, lifestyle

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