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Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire.
Andreu-Sánchez, Sergio; Bourgonje, Arno R; Vogl, Thomas; Kurilshikov, Alexander; Leviatan, Sigal; Ruiz-Moreno, Angel J; Hu, Shixian; Sinha, Trishla; Vich Vila, Arnau; Klompus, Shelley; Kalka, Iris N; de Leeuw, Karina; Arends, Suzanne; Jonkers, Iris; Withoff, Sebo; Brouwer, Elisabeth; Weinberger, Adina; Wijmenga, Cisca; Segal, Eran; Weersma, Rinse K; Fu, Jingyuan; Zhernakova, Alexandra.
Afiliación
  • Andreu-Sánchez S; 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.
  • Bourgonje AR; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Vogl T; 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
  • Kurilshikov A; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Leviatan S; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Ruiz-Moreno AJ; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Hu S; 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.
  • Sinha T; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Vich Vila A; 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.
  • Klompus S; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Kalka IN; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
  • de Leeuw K; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Arends S; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Jonkers I; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Withoff S; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Brouwer E; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Weinberger A; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Wijmenga C; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Segal E; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Weersma RK; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Fu J; 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.
  • Zhernakova A; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: sashazhernakova@gmail.com.
Immunity ; 56(6): 1376-1392.e8, 2023 06 13.
Article en En | MEDLINE | ID: mdl-37164013
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacteriófagos / Anticuerpos Límite: Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacteriófagos / Anticuerpos Límite: Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos