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

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 antiflagellin 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.

Automated summary

Microbial exposures play a crucial role in impacting healthspan through shaping the immune system and microbiota. The use of Phage ImmunoPrecipitation Sequencing (PhIP-Seq) allows for high-throughput and cost-effective detection of exposure and response to microbial protein products. This study demonstrates that PhIP-Seq with the ToxScan library is an effective tool for studying the environmental determinants of health and disease at a cohort scale.