Longitudinal T cell repertoire analysis reveals dynamic clonal T cell populations in Ulcerative Colitis.

Background: Ulcerative Colitis (UC) is characterized by chronic, relapsing and remitting inflammation in the colon and rectum. Pathogenic T cell activity is thought to play a major role in this process. T cell effector function is determined by the T cell receptor (TCR) and the antigen it recognizes. Examining the TCR repertoire can provide key insights into the adaptive immune response.

Objective: To characterize the longitudinal TCR repertoire of patients with UC across disease activity to determine if recurrent antigen(s) are responsible for active inflammation.

Design: Bulk TCR Vβ sequencing was done on colon tissue of 20 patients with UC across multiple time points of disease. Corresponding clinical metadata was also obtained over the same time period for each patient to map their clinical disease course. The top ten most highly abundant clones from each time point were longitudinally tracked and correlated with disease phenotype.

Results: Seventy-five percent of patients did not have overlapping abundant TCR clones across multiple time points of disease. The remaining 25% of patients had one to five TCR clones present in high abundance in their tissue during every time point analyzed.

Conclusion: These results demonstrate that most patients with UC do not share a similar TCR repertoire over time, indicating that times of inflammation are associated with unique antigen exposures. A smaller group of patients have persistent, private TCR clones with high abundance, 60% of whom had more unremitting, active disease.