Increased Nur77 is disconnected from TCR affinity in insulin-specific Tregs
- 1Department of Pathology, Division of Microbiology and Immunology, University of Utah , Salt Lake City, UT,
- 2Section of Diabetes and Endocrinology, Department of Pediatrics, Texas Children’s Hospital, Baylor College of Medicine , Houston, TX,
Abstract
Foxp3+ regulatory T cells (Tregs) are capable suppressors of aberrant self-reactivity. However, how differences in affinity and specificity may support Treg function compared with autoimmune T cell function remains unresolved. In this study, we analyzed the T cell receptor (TCR) repertoires of the regulatory and effector T cells that spontaneously infiltrate pancreatic islets of nonobese diabetic mice and therefore share antigen specificity. Using 2-dimensional micropipette measurements of TCR affinity, we show that effector and regulatory T cell-derived TCRs possess similar wide-ranging affinities for self-antigen. Treg-derived TCRs conferred variable protective function and Treg suppressive capacity was, in part, determined by the relative antigen-reactivity of effector T cells. Interestingly, when expressing the same TCR, Tregs showed higher Nur77-GFP expression than effector T cells in vivo, suggesting a Treg-intrinsic ability to compete for antigen. In vitro, we observed accelerated Treg TCR activation, suggesting that Tregs are poised for faster response to antigen than T effectors. Our findings expose a subpopulation of Tregs possessing low-affinity, suboptimal TCRs, obscured by apparent higher Nur77 expression in Tregs as a whole.
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BibTeX
@article{jing2026increased,
title = {{Increased Nur77 is disconnected from TCR affinity in insulin-specific Tregs}},
author = {Yi Jing and Yuelin Kong and Baoyu Liu and Elizabeth Motunrayo Kolawole and Tessa Galland and L Gillen and M Kenison and Maran L. Sprouse and Brian D. Evavold and M Bettini and Maria Bettini},
journal = {The Journal of Immunology},
year = {2026},
month = jun,
doi = {10.1093/jimmun/vkag136},
url = {https://doi.org/10.1093/jimmun/vkag136},
note = {CC BY},
}
RIS
TY - JOUR
TI - Increased Nur77 is disconnected from TCR affinity in insulin-specific Tregs
AU - Yi Jing
AU - Yuelin Kong
AU - Baoyu Liu
AU - Elizabeth Motunrayo Kolawole
AU - Tessa Galland
AU - L Gillen
AU - M Kenison
AU - Maran L. Sprouse
AU - Brian D. Evavold
AU - M Bettini
AU - Maria Bettini
PY - 2026
DA - 2026/06/01
JO - The Journal of Immunology
DO - 10.1093/jimmun/vkag136
UR - https://doi.org/10.1093/jimmun/vkag136
AB - Foxp3+ regulatory T cells (Tregs) are capable suppressors of aberrant self-reactivity. However, how differences in affinity and specificity may support Treg function compared with autoimmune T cell function remains unresolved. In this study, we analyzed the T cell receptor (TCR) repertoires of the regulatory and effector T cells that spontaneously infiltrate pancreatic islets of nonobese diabetic mice and therefore share antigen specificity. Using 2-dimensional micropipette measurements of TCR affinity, we show that effector and regulatory T cell-derived TCRs possess similar wide-ranging affinities for self-antigen. Treg-derived TCRs conferred variable protective function and Treg suppressive capacity was, in part, determined by the relative antigen-reactivity of effector T cells. Interestingly, when expressing the same TCR, Tregs showed higher Nur77-GFP expression than effector T cells in vivo, suggesting a Treg-intrinsic ability to compete for antigen. In vitro, we observed accelerated Treg TCR activation, suggesting that Tregs are poised for faster response to antigen than T effectors. Our findings expose a subpopulation of Tregs possessing low-affinity, suboptimal TCRs, obscured by apparent higher Nur77 expression in Tregs as a whole.
SN - 0022-1767
SN - 1550-6606
ER -