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

Lifelines Cohort Study; Sergio Andreu-Sánchez; Arno R. Bourgonje; Thomas Vogl; Aleksandr Kurilshchikov; 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

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

Lifelines Cohort Study, Sergio Andreu-Sánchez, Arno R. Bourgonje, Thomas Vogl^*, Aleksandr Kurilshchikov, 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 SegalRinse K. Weersma, Jingyuan Fu, Alexandra Zhernakova

^*Bijbehorende auteur voor dit werk

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Samenvatting

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.

Originele taal-2	English
Pagina's (van-tot)	1376-1392.e8
Aantal pagina's	26
Tijdschrift	Immunity
Volume	56
Nummer van het tijdschrift	6
Vroegere onlinedatum	9-mei-2023
DOI's	https://doi.org/10.1016/j.immuni.2023.04.003
Status	Published - 13-jun.-2023

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Phage display sequencing reveals
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Lifelines Cohort Study, Andreu-Sánchez, S., Bourgonje, A. R., Vogl, T., Kurilshchikov, A., Leviatan, S., Ruiz-Moreno, A. J., Hu, S., Sinha, T., Vich Vila, A., Klompus, S., Kalka, I. N., de Leeuw, K., Arends, S., Jonkers, I., Withoff, S., Brouwer, E., Weinberger, A., Wijmenga, C., ... Zhernakova, A. (2023). Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire. Immunity, 56(6), 1376-1392.e8. Advance online publication. https://doi.org/10.1016/j.immuni.2023.04.003

@article{13b8fc5620c64a54a0419f37cdc28050,

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

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 = "Humans, Epitopes/genetics, Antibodies, Antigens, Peptides, Bacteriophages",

author = "{Lifelines Cohort Study} and Sergio Andreu-S{\'a}nchez and Bourgonje, {Arno R.} and Thomas Vogl and Aleksandr Kurilshchikov and Sigal Leviatan and Ruiz-Moreno, {Angel J.} and Shixian Hu and Trishla Sinha and {Vich Vila}, Arnau and Shelley Klompus and Kalka, {Iris N.} and {de Leeuw}, Karina and Suzanne Arends and Iris Jonkers and Sebo Withoff and Elisabeth Brouwer and Adina Weinberger and Cisca Wijmenga and Eran Segal and Weersma, {Rinse K.} and Jingyuan Fu and Alexandra Zhernakova",

year = "2023",

month = jun,

day = "13",

doi = "10.1016/j.immuni.2023.04.003",

language = "English",

volume = "56",

pages = "1376--1392.e8",

journal = "Immunity",

issn = "1074-7613",

publisher = "CELL PRESS",

number = "6",

}

Lifelines Cohort Study, Andreu-Sánchez, S , Bourgonje, AR, Vogl, T, Kurilshchikov, A, Leviatan, S, Ruiz-Moreno, AJ , Hu, S , Sinha, T , Vich Vila, A, Klompus, S, Kalka, IN, de Leeuw, K , Arends, S , Jonkers, I , Withoff, S , Brouwer, E, Weinberger, A, Wijmenga, C, Segal, E, Weersma, RK , Fu, J & Zhernakova, A 2023, 'Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire', Immunity, vol. 56, nr. 6, blz. 1376-1392.e8. https://doi.org/10.1016/j.immuni.2023.04.003

TY - JOUR

T1 - Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire

AU - Lifelines Cohort Study

AU - Andreu-Sánchez, Sergio

AU - Bourgonje, Arno R.

AU - Vogl, Thomas

AU - Kurilshchikov, Aleksandr

AU - Leviatan, Sigal

AU - Ruiz-Moreno, Angel J.

AU - Hu, Shixian

AU - Sinha, Trishla

AU - Vich Vila, Arnau

AU - Klompus, Shelley

AU - Kalka, Iris N.

AU - de Leeuw, Karina

AU - Arends, Suzanne

AU - Jonkers, Iris

AU - Withoff, Sebo

AU - Brouwer, Elisabeth

AU - Weinberger, Adina

AU - Wijmenga, Cisca

AU - Segal, Eran

AU - Weersma, Rinse K.

AU - Fu, Jingyuan

AU - Zhernakova, Alexandra

PY - 2023/6/13

Y1 - 2023/6/13

N2 - 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.

AB - 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.

KW - Humans

KW - Epitopes/genetics

KW - Antibodies

KW - Antigens

KW - Peptides

KW - Bacteriophages

U2 - 10.1016/j.immuni.2023.04.003

DO - 10.1016/j.immuni.2023.04.003

M3 - Review article

C2 - 37164013

SN - 1074-7613

VL - 56

SP - 1376-1392.e8

JO - Immunity

JF - Immunity

IS - 6

ER -