Mapping the T cell repertoire to a complex defined gut bacterial community
نویسندگان
چکیده
Abstract Certain bacterial strains from the microbiome induce a potent, antigen-specific T cell response. Previous reports have profiled gut under artificial conditions of mono-colonization. While this approach can identify that potential to modulate immune function, it does not reveal how strain behaves in physiological context complex community. Here, we colonize germ-free mice with defined community (>100 strains) and profile responses each individually. Unexpectedly, pattern suggests many cells repertoire recognize multiple We constructed hybridomas 92 receptor (TCR) clonotypes; by screening every against hybridoma, find nearly all bacteria-specific TCRs exhibit one-to-many TCR-to-strain relationship, including 13 abundant TCR clonotypes are polyspecific for 18 Firmicutes By three pooled genomic libraries hybridomas, discover they share single target: conserved substrate-binding protein (SBP) an ABC transport system. Treg Th17 specific epitope community-colonized specific-pathogen-free mice. Our work reveals recognition is focused on widely cell-surface antigen, opening door new therapeutic strategies which colonist-specific rationally altered or redirected. This was supported Stanford Microbiome Therapies Initiative, Human Frontier Science Program LT000493/2018-L (K.N.), Fellowship Astellas Foundation Research Metabolic Disorders research grant Kanae Fundation Promotion Medical HHMI-Simons Faculty Scholar Award (M.A.F.); Leona M. Harry B. Helmsley Charitable Trust NIH DK110174 Chan Zuckerberg Biohub Stand Up Cancer MAC3 Impact Philanthropies (M.A.F.).
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.218.12