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【Seminar Report】WPI-Bio2Q Open Seminar: Kazuki Nagashima, MD-PhD

August 18, 2025

August 18, 2025

Keio University Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q) held a seminar as follows.

17:00 -18:00 August 7, 2025

Venue: 1F Lounge, Center for Integrated Medical Research, Shinanomachi Campus, Keio University

Speaker:
Kazuki Nagashima, MD-PhD
Assistant Professor
Department of Molecular and Cellular Biology
Harvard University, USA

Title: “Mapping the T cell repertoire to a model system of the human gut microbiome”

Certain gut bacteria elicit strong, antigen-specific T cell responses. While past studies used mono-colonization to identify immunomodulatory strains, this doesn’t reflect how strains behave within complex communities. We colonized germ-free mice with a defined >100-strain community and profiled T cell responses to each strain. Surprisingly, many T cells recognized multiple strains. Screening 92 TCR hybridomas revealed that most TCRs were polyspecific, including 13 abundant clonotypes targeting 18 Firmicutes. These TCRs shared a conserved antigen: a substrate-binding protein (SBP) from an ABC transporter. Treg and Th17 cells specific for the SBP are abundant in community-colonized and SPF mice. 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.

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