TY - JOUR
T1 - Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire
AU - Andreu-Sánchez, Sergio
AU - Bourgonje, Arno R.
AU - Vogl, Thomas
AU - Kurilshikov, Alexander
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.
N1 - Publisher Copyright: © 2023 Elsevier Inc.
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.
UR - http://www.scopus.com/inward/record.url?scp=85161296860&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2023.04.003
DO - 10.1016/j.immuni.2023.04.003
M3 - مقالة
SN - 1074-7613
VL - 56
SP - 1376
EP - 1392
JO - Immunity
JF - Immunity
IS - 6
ER -