Expanded TCRβ CDR3 clonotypes distinguish Crohn's disease and ulcerative colitis patients

• Published in: Mucosal immunology Vol. 11; no. 5; pp. 1487 - 1495
• Main Authors: Wu, J., Pendegraft, A.H., Byrne-Steele, M., Yang, Q., Wang, C., Pan, W., Lucious, T., Seay, T., Cui, X., Elson, C.O., Han, J., Mannon, P.J.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.09.2018; Nature Publishing Group US; Elsevier Limited
• Subjects: Allergology; Antibodies; Antigens; Antigens - immunology; Biomedical and Life Sciences; Biomedicine; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell Line; Cell proliferation; Cell Proliferation - physiology; Colitis, Ulcerative - immunology; Complementarity-determining region 3; Crohn Disease - immunology; Crohn's disease; Flagellin; Flagellin - immunology; Gastroenterology; Humans; Immunology; Inflammatory bowel disease; Intestinal microflora; Leukocytes, Mononuclear - immunology; Lymphocytes T; Receptors, Antigen, T-Cell, alpha-beta - immunology; T cell receptors; Ulcerative colitis
• ISSN: 1933-0219; 1935-3456; 1935-3456
• DOI: 10.1038/s41385-018-0046-z

We aimed to determine whether the TCR repertoires of Crohn's disease (CD) patients contain highly prevalent disease-specific T-cell clonotypes reflective of the characteristic and highly shared aberrant serum antibody reactivity to gut commensal flagellin antigens. The CD4 TCRβ CDR3 sequence repertoires from active CD (n = 20) and ulcerative colitis (UC) (n = 10) patients were significantly more diverse, and individual sequences over-represented, compared to healthy controls (HC) (n = 97). While a very small number of expanded public CDR3 sequences are highly shared between active CD and UC, the majority of significantly expanded TCRβ CDR3 clonotypes are private to CD and UC patients with equivalent prevalence among IBD patients. Further defining TCR clonotypes by Vβ-CDR3 linkage showed significant differences in the TCR repertoires between UC and CD. Flagellin antigen exposure induced expansion of several TCRβ CDR3 sequences in CD4 cells from a flagellin-seropositive subject including sequences highly shared by or relatively private to CD (and UC) patients. These data suggest that flagellin-reactivity contributes to the expansion of a small number of CD4 clonotypes but does not support flagellin antigens as predominantly driving CD4 cell proliferation in CD. Disease-specific expanded TCRβ CDR3 clonotypes characterize CD and UC and the shared exposure to the gamut of gut microbial antigens.