Circulating gluten-specific, but not CMV-specific, CD39(+) regulatory T cells have an oligoclonal TCR repertoire
AuthorCook, L; Munier, CML; Seddiki, N; Hardy, MY; Anderson, RP; Zaunders, J; Tye-Din, JA; Kelleher, AD; van Bockel, D
Source TitleClinical and Translational Immunology
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsCook, L., Munier, C. M. L., Seddiki, N., Hardy, M. Y., Anderson, R. P., Zaunders, J., Tye-Din, J. A., Kelleher, A. D. & van Bockel, D. (2020). Circulating gluten-specific, but not CMV-specific, CD39(+) regulatory T cells have an oligoclonal TCR repertoire. CLINICAL & TRANSLATIONAL IMMUNOLOGY, 9 (1), https://doi.org/10.1002/cti2.1096.
Access StatusOpen Access
Objectives: Understanding the T cell receptor (TCR) repertoire of regulatory CD4+ T-cell (Treg) populations is important for strategies aiming to re-establish tolerance in autoimmune diseases. We studied circulating deamidated gluten-epitope-specific CD39+ Tregs in patients with coeliac disease following an oral gluten challenge, and we used cytomegalovirus (CMV)-specific CD39+ Tregs from healthy controls as a comparator population. Methods: We used the OX40 assay to isolate antigen-specific Tregs by induced surface co-expression of CD25, OX40 and CD39. RACE PCR amplification and Sanger sequencing of the TCR β chain were used to analyse repertoire diversity. Results: We found that, following oral gluten challenge, circulating gluten-specific CD39+ Tregs had an oligoclonal TCR repertoire that contained public clonotypes. Conversely, the TCR repertoire of CMV-epitope-specific CD39+ Tregs from healthy controls was polyclonal. Discussion: These data indicate that a biased TCR repertoire is not inherent to CD39+ Tregs, and, in this case, is apparently driven by the HLA-DQ2.5-restricted deamidated gluten peptide in coeliac disease patients. Conclusion: This is the first assessment of the TCR repertoire within circulating human Tregs specific for foreign antigen. These data enhance our understanding of antigen-specific CD4+ responses in the settings of chronic inflammation and infection and may help guide immunomonitoring strategies for CD4+ T cell-based therapies, particularly for coeliac disease.
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