Phage display of environmental protein toxins and virulence factors reveals the prevalence, persistence, and genetics of antibody responses.
Crohn's
ToxScan
antibody epitoe profiling
disease
humoral immunity
immunogenetics
juvenile dermatomyositis
microbiome
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
14 06 2022
14 06 2022
Historique:
received:
03
09
2021
revised:
17
02
2022
accepted:
03
05
2022
pubmed:
2
6
2022
medline:
18
6
2022
entrez:
1
6
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35649416
pii: S1074-7613(22)00222-9
doi: 10.1016/j.immuni.2022.05.002
pmc: PMC9203978
mid: NIHMS1807320
pii:
doi:
Substances chimiques
Antibodies
0
Immunodominant Epitopes
0
Peptide Library
0
Virulence Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1051-1066.e4Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK114252
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM136724
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM136577
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests H.B.L. is an inventor on an issued patent (US20160320406A) filed by Brigham and Women’s Hospital that covers the use of the VirScan technology; is a founder of ImmuneID, Portal Bioscience, and Alchemab; and is an advisor to TScan Therapeutics. C.L.S. is supported for unrelated work by research grants from Janssen and Bristol Myers Squibb.
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