Objective: Inflammatory Bowel Diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are known to involve shifts in the T-cell repertoires of affected individuals, including clonal expansion of abundant T-cell populations in CD mucosal tissue. There are also differential HLA risk and protective alleles between CD and UC, implying CD- and UC-specific repertoire changes that have not yet been identified. In this study we aimed to identify specific, antigen-driven T cell signatures in CD and UC.

Methods: We performed ImmunoSequencing on blood samples from 3,853 CD cases, 1,803 UC cases, and 5,596 healthy controls. We identified public TCRBs significantly enriched in CD or UC cases.

Results: We determine that there is more expansion across clonotypes in CD, but not UC, compared with healthy controls. Strikingly, from blood we identify public TCRBs specifically expanded in CD or UC. These sequences are more abundant in intestinal mucosal samples, form groups of similar CDR3 sequences, and can be associated to specific HLA alleles. Although the prevalence of these sequences is higher in ileal and ileocolonic CD than colonic CD or UC, the TCRB sequences themselves are shared across CD and not between CD and UC.

Conclusions: There are peptide antigens that commonly evoke immune reactions in IBD cases and rarely in non-IBD controls. These antigens differ between CD and UC. CD, particularly ileal CD, also seems to involve more substantial changes in clonal population structure than UC, compared to healthy controls.