Phage display of environmental protein toxins and virulence factors reveals the prevalence, persistence, and genetics of antibody responses

Immunity. 2022 Jun 14;55(6):1051-1066.e4. doi: 10.1016/j.immuni.2022.05.002. Epub 2022 May 31.

Abstract

Microbial exposures are crucial environmental factors that impact healthspan by sculpting the immune system and microbiota. Antibody profiling via Phage ImmunoPrecipitation Sequencing (PhIP-Seq) provides a high-throughput, cost-effective approach for detecting exposure and response to microbial protein products. We designed and constructed a library of 95,601 56-amino acid peptide tiles spanning 14,430 proteins with "toxin" or "virulence factor" keyword annotations. We used PhIP-Seq to profile the antibodies of ∼1,000 individuals against this "ToxScan" library. In addition to enumerating immunodominant antibody epitopes, we studied the age-dependent stability of the ToxScan profile and used a genome-wide association study to find that the MHC-II locus modulates bacterial epitope selection. We detected previously described anti-flagellin antibody responses in a Crohn's disease cohort and identified an association between anti-flagellin antibodies and juvenile dermatomyositis. PhIP-Seq with the ToxScan library is thus an effective tool for studying the environmental determinants of health and disease at cohort scale.

Keywords: Crohn's; ToxScan; antibody epitoe profiling; disease; humoral immunity; immunogenetics; juvenile dermatomyositis; microbiome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies
  • Antibody Formation
  • Bacteriophages* / genetics
  • Genome-Wide Association Study
  • Humans
  • Immunodominant Epitopes
  • Peptide Library*
  • Prevalence
  • Virulence Factors / genetics

Substances

  • Antibodies
  • Immunodominant Epitopes
  • Peptide Library
  • Virulence Factors