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

Julia W. Angkeow; Daniel R. Monaco; Athena Chen; Thiagarajan Venkataraman; Sahana Jayaraman; Cristian Valencia; Brandon M. Sie; Thomas Liechti; Payam N. Farhadi; Gabriela Funez-dePagnier; Cheryl A. Sherman-Baust; May Q. Wong; Ingo Ruczinski; Patrizio Caturegli; Cynthia L. Sears; Patricia J. Simner; June L. Round; Priya Duggal; Uri Laserson; Theodore S. Steiner; Ranjan Sen; Thomas E. Lloyd; Mario Roederer; Andrew L. Mammen; Randy S. Longman; Lisa G. Rider; H. Benjamin Larman

doi:10.1016/j.immuni.2022.05.002

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

Julia W. Angkeow, Daniel R. Monaco, Athena Chen, Thiagarajan Venkataraman, Sahana Jayaraman, Cristian Valencia, Brandon M. Sie, Thomas Liechti, Payam N. Farhadi, Gabriela Funez-dePagnier, Cheryl A. Sherman-Baust, May Q. Wong, Ingo Ruczinski, Patrizio Caturegli, Cynthia L. Sears, Patricia J. Simner, June L. Round, Priya Duggal, Uri Laserson, Theodore S. SteinerRanjan Sen, Thomas E. Lloyd, Mario Roederer, Andrew L. Mammen, Randy S. Longman, Lisa G. Rider, H. Benjamin Larman

Genetics and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English
Pages (from-to)	1051-1066.e4
Journal	Immunity
Volume	55
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2022.05.002
State	Published - 14 Jun 2022

Keywords

Crohn's
ToxScan
antibody epitoe profiling
disease
humoral immunity
immunogenetics
juvenile dermatomyositis
microbiome

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10.1016/j.immuni.2022.05.002

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Angkeow, J. W., Monaco, D. R., Chen, A., Venkataraman, T., Jayaraman, S., Valencia, C., Sie, B. M., Liechti, T., Farhadi, P. N., Funez-dePagnier, G., Sherman-Baust, C. A., Wong, M. Q., Ruczinski, I., Caturegli, P., Sears, C. L., Simner, P. J., Round, J. L., Duggal, P., Laserson, U., ... Larman, H. B. (2022). Phage display of environmental protein toxins and virulence factors reveals the prevalence, persistence, and genetics of antibody responses. Immunity, 55(6), 1051-1066.e4. https://doi.org/10.1016/j.immuni.2022.05.002

@article{0561610dff8e45578dd48189f595ffde,

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

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",

author = "Angkeow, {Julia W.} and Monaco, {Daniel R.} and Athena Chen and Thiagarajan Venkataraman and Sahana Jayaraman and Cristian Valencia and Sie, {Brandon M.} and Thomas Liechti and Farhadi, {Payam N.} and Gabriela Funez-dePagnier and Sherman-Baust, {Cheryl A.} and Wong, {May Q.} and Ingo Ruczinski and Patrizio Caturegli and Sears, {Cynthia L.} and Simner, {Patricia J.} and Round, {June L.} and Priya Duggal and Uri Laserson and Steiner, {Theodore S.} and Ranjan Sen and Lloyd, {Thomas E.} and Mario Roederer and Mammen, {Andrew L.} and Longman, {Randy S.} and Rider, {Lisa G.} and Larman, {H. Benjamin}",

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

month = jun,

day = "14",

doi = "10.1016/j.immuni.2022.05.002",

language = "English",

volume = "55",

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Angkeow, JW, Monaco, DR, Chen, A, Venkataraman, T, Jayaraman, S, Valencia, C, Sie, BM, Liechti, T, Farhadi, PN, Funez-dePagnier, G, Sherman-Baust, CA, Wong, MQ, Ruczinski, I, Caturegli, P, Sears, CL, Simner, PJ, Round, JL, Duggal, P, Laserson, U, Steiner, TS, Sen, R, Lloyd, TE, Roederer, M, Mammen, AL, Longman, RS, Rider, LG & Larman, HB 2022, 'Phage display of environmental protein toxins and virulence factors reveals the prevalence, persistence, and genetics of antibody responses', Immunity, vol. 55, no. 6, pp. 1051-1066.e4. https://doi.org/10.1016/j.immuni.2022.05.002

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AU - Angkeow, Julia W.

AU - Monaco, Daniel R.

AU - Chen, Athena

AU - Venkataraman, Thiagarajan

AU - Jayaraman, Sahana

AU - Valencia, Cristian

AU - Sie, Brandon M.

AU - Liechti, Thomas

AU - Farhadi, Payam N.

AU - Funez-dePagnier, Gabriela

AU - Sherman-Baust, Cheryl A.

AU - Wong, May Q.

AU - Ruczinski, Ingo

AU - Caturegli, Patrizio

AU - Sears, Cynthia L.

AU - Simner, Patricia J.

AU - Round, June L.

AU - Duggal, Priya

AU - Laserson, Uri

AU - Steiner, Theodore S.

AU - Sen, Ranjan

AU - Lloyd, Thomas E.

AU - Roederer, Mario

AU - Mammen, Andrew L.

AU - Longman, Randy S.

AU - Rider, Lisa G.

AU - Larman, H. Benjamin

PY - 2022/6/14

Y1 - 2022/6/14

N2 - 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.

AB - 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.

KW - Crohn's

KW - ToxScan

KW - antibody epitoe profiling

KW - disease

KW - humoral immunity

KW - immunogenetics

KW - juvenile dermatomyositis

KW - microbiome

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U2 - 10.1016/j.immuni.2022.05.002

DO - 10.1016/j.immuni.2022.05.002

M3 - Article

C2 - 35649416

AN - SCOPUS:85131801924

SN - 1074-7613

VL - 55

SP - 1051-1066.e4

JO - Immunity

JF - Immunity

IS - 6

ER -

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

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Keywords

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