Circulating gluten-specific, but not CMV-specific, CD39(+) regulatory T cells have an oligoclonal TCR repertoire

Cook, L; Munier, CML; Seddiki, N; Hardy, MY; Anderson, RP; Zaunders, J; Tye-Din, JA; Kelleher, AD; van Bockel, D

Author(s): Cook, L; Munier, CML; Seddiki, N; Hardy, MY; Anderson, RP; Zaunders, J; Tye-Din, JA; Kelleher, AD; van Bockel, D;
Details: Publication Year 2020,Volume 9,Issue #1,Page e1096
Journal Title: Clinicical & Translational Immunology
Publication Type: Journal Article
Abstract: 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 beta 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.
Publisher: Wiley
Research Division(s): Immunology
PubMed ID: 31956412
Link To PubMed Central Version: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955237/
Publisher's Version: https://doi.org/10.1002/cti2.1096
Open Access at Publisher's Site: https://doi.org/10.1002/cti2.1096
NHMRC Grants: NHMRC/510448, NHMRC/1085875,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2020-02-24 09:55:57

Last Modified: 2020-02-24 10:02:25