Immunity · 2022
Phage display of environmental protein toxins and virulence factors reveals the prevalence, persistence, and genetics of antibody responses.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Angkeow Julia W, Monaco Daniel R, Chen Athena, Venkataraman Thiagarajan, Jayaraman Sahana, Valencia Cristian, Sie Brandon M, Liechti Thomas, Farhadi Payam N, Funez-dePagnier Gabriela, Sherman-Baust Cheryl A, Wong May Q, Ruczinski Ingo, Caturegli Patrizio, Sears Cynthia L, Simner Patricia J, Round June L, Duggal Priya, Laserson Uri, Steiner Theodore S, Sen Ranjan, Lloyd Thomas E, Roederer Mario, Mammen Andrew L, Longman Randy S, Rider Lisa G, Larman H Benjamin
Аннотация
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.