2/27, LSBM Monday Seminar Series #20, Kazuki Nagashima, Mapping the T cell repertoire to a complex gut bacterial community

Presenter: Kazuki Nagashima

Affiliation: Senior Research Scientist, Michael Fischbach Lab, Department of Bioengineering, Stanford University, USA

Title: Mapping the T cell repertoire to a complex gut bacterial community

 

 

Abstract: Certain bacterial strains from the microbiome induce a potent T cell response. Previous studies have been performed under the artificial conditions of mono-colonization, but we lack an understanding of how each strain modulates the immune system in the physiologic setting of a native-scale bacterial community. Here, we colonize germ-free mice with a complex defined community (112 bacterial strains) and profile T cell responses to each strain individually. Unexpectedly, the pattern of T cell responses suggests that many T cells in the gut repertoire recognize multiple bacterial strains from the community. We constructed T cell hybridomas from 92 T cell receptor (TCR) clonotypes; by screening every strain in the community against each hybridoma, we find that nearly all of the bacteria-specific TCRs exhibit a one-to-many TCR-to-strain relationship, including 13 abundant TCR clonotypes that are polyspecific for 18 Firmicutes in the community. By screening bacterial genomic libraries against Firmicutes-specific hybridomas, we discover that they share a single target: a conserved substrate-binding protein (SBP) from an ABC transport system. Our work reveals that T cell recognition of Firmicutes is focused on a widely conserved cell-surface antigen, opening the door to new therapeutic strategies in which colonist-specific immune responses are rationally altered or redirected.

 

 

 

References:

1) Nagashima et al., Mapping the T cell repertoire to a complex gut bacterial community, bioRxiv, 2022

2) Cheng et al., Design, construction, and in vivo augmentation of a complex gut microbiome, Cell, 2022.

3) Guo et al., Depletion of microbiome-derived molecules in the host using Clostridium genetics, Science, 2019

4) Nagashima et al., Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota, Nature Immunology, 2017

 

 

 

[略歴]

2013年 東京大学医学部医学科 卒業

2017年 東京大学医学部医学系研究科免疫学 博士課程修了(高柳 広 教授)

2017年 Post-Doctoral Scholar, Michael Fischbach Lab, Department of Bioengineering, Stanford University, USA

2022年 Senior Research Scientist, Michael Fischbach Lab, Department of Bioengineering, Stanford University, USA