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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
Published on: January 12, 2021
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Mapping the T cell repertoire to a complex gut bacterial community
Kazuki Nagashima1,2,3, Aishan Zhao1,2,3, Katayoon Atabakhsh1,2,3
1Department of Bioengineering, Stanford University, Stanford, CA, USA.
Nature
|August 16, 2023
Summary
Gut bacteria T cells often recognize multiple strains, not just one. Researchers found T cells target conserved proteins on bacteria, offering new therapeutic strategies for immune responses.
Area of Science:
- Immunology
- Microbiome Research
- T cell Biology
Background:
- Microbiome bacteria stimulate potent T cell responses.
- Specificity of T cells to individual bacterial strains is not well understood.
Purpose of the Study:
- To investigate the strain-level specificity of T cell responses within complex gut microbial communities.
- To identify the antigens recognized by microbiome-specific T cells.
Main Methods:
- Colonization of germ-free mice with defined microbial communities.
- Profiling T cell responses to individual bacterial strains.
- T cell receptor (TCR) hybridoma construction and screening.
- Genomic library screening to identify conserved bacterial targets.
Main Results:
- Many gut T cells recognize multiple bacterial strains.
- Most bacteria-specific TCRs exhibit a one-to-many relationship with bacterial strains.
- A conserved substrate-binding protein was identified as a common target for multiple TCRs.
- Specific T cells targeting this protein are abundant in mice.
Conclusions:
- T cell recognition of gut commensals focuses on conserved, highly expressed antigens.
- This conserved recognition pattern has implications for therapeutic strategies.
- Potential for rationally altering or redirecting colonist-specific immune responses.
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