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Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells
Published on: September 18, 2016
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Longitudinal T cell repertoire analysis reveals dynamic clonal T cell populations in Ulcerative Colitis
Biorxiv : the Preprint Server for Biology
|January 27, 2025
Summary
Most ulcerative colitis (UC) patients show unique T cell receptor (TCR) repertoires during inflammation, suggesting diverse antigen triggers. A subset, however, exhibits persistent TCR clones linked to unremitting disease.
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- Ulcerative colitis (UC) involves chronic inflammation of the colon and rectum.
- T cell activity and T cell receptor (TCR) recognition of antigens are crucial in UC pathogenesis.
- Analyzing the TCR repertoire offers insights into the adaptive immune response in UC.
Purpose of the Study:
- To longitudinally characterize the TCR repertoire in UC patients.
- To determine if specific antigens trigger recurrent inflammation in UC.
- To correlate TCR repertoire dynamics with disease activity and phenotype.
Main Methods:
- Bulk TCR Vβ sequencing of colon tissue from 20 UC patients.
- Longitudinal sampling across multiple disease activity time points.
- Correlation of abundant TCR clones with clinical metadata and disease course.
Main Results:
- 75% of patients lacked overlapping abundant TCR clones across time points.
- 25% of patients displayed 1-5 persistent, highly abundant TCR clones throughout the study.
- Persistent TCR clones were associated with more unremitting disease in 60% of these patients.
Conclusions:
- Most UC patients exhibit dynamic TCR repertoires, implying varied antigen exposures during inflammation.
- A distinct subgroup of UC patients harbors persistent TCR clones, potentially linked to chronic or severe disease.
- TCR repertoire analysis can reveal patient-specific immune responses in ulcerative colitis.
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