ArticleJournal of immunology (Baltimore, Md. : 1950)2014
TCR affinity and tolerance mechanisms converge to shape T cell diabetogenic potential.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Increased Nur77 is disconnected from TCR affinity in insulin-specific Tregs.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- CD4Immunity · 2024Article
- Crinophagic granules in pancreatic β cells contribute to mouse autoimmune diabetes by diversifying pathogenic epitope repertoire.Nature communications · 2024Article
- Tumor-Reactive CD8+ T Cells Enter a TCF1+PD-1- Dysfunctional State.Cancer immunology research · 2023Article
- The amphiregulin/EGFR axis has limited contribution in controlling autoimmune diabetes.Scientific reports · 2023Article
- A dormant T-cell population with autoimmune potential exhibits low self-reactivity and infiltrates islets in type 1 diabetes.European journal of immunology · 2022Article
- T cell help in the autoreactive germinal center.Scandinavian journal of immunology · 2022Review
- T-Cell Receptor/HLA Humanized Mice Reveal Reduced Tolerance and Increased Immunogenicity of Posttranslationally Modified GAD65 Epitope.Diabetes · 2022Article
- TIGIT as a Promising Therapeutic Target in Autoimmune Diseases.Frontiers in immunology · 2022Review
- Strength and Numbers: The Role of Affinity and Avidity in the 'Quality' of T Cell Tolerance.Cells · 2021Review
- Relationship of 2D Affinity to T Cell Functional Outcomes.International journal of molecular sciences · 2020Review
- A Hybrid Insulin Epitope Maintains High 2D Affinity for Diabetogenic T Cells in the Periphery.Diabetes · 2020Article
- A Critical Insulin TCR Contact Residue Selects High-Affinity and Pathogenic Insulin-Specific T Cells.Diabetes · 2020Article
- Type 1 diabetes pathogenesis and the role of inhibitory receptors in islet tolerance.Annals of the New York Academy of Sciences · 2020Review
- A Novel Animal Model of Emphysema Induced by Anti-Elastin Autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- TCR Retrogenic Mice as a Model To Map Self-Tolerance Mechanisms to the Cancer Mucosa Antigen GUCY2C.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- CD4 T Cells Reactive to Hybrid Insulin Peptides Are Indicators of Disease Activity in the NOD Mouse.Diabetes · 2018Article
- Cutting Edge: Low-Affinity TCRs Support Regulatory T Cell Function in Autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- High self-reactivity drives T-bet and potentiates Treg function in tissue-specific autoimmunity.JCI insight · 2018Article
- Evolving Approaches in the Identification of Allograft-Reactive T and B Cells in Mice and Humans.Transplantation · 2017Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Autoreactive T cells infiltrating the target organ can possess a broad TCR affinity range. However, the extent to which such biophysical parameters contribute to T cell pathogenic potential remains unclear. In this study, we selected eight InsB9-23-specific TCRs cloned from CD4(+) islet-infiltrating T cells that possessed a relatively broad range of TCR affinity to generate NOD TCR retrogenic mice. These TCRs exhibited a range of two-dimensional affinities (∼ 10(-4)-10(-3) μm(4)) that correlated with functional readouts and responsiveness to activation in vivo. Surprisingly, both higher and lower affinity TCRs could mediate potent insulitis and autoimmune diabetes, suggesting that TCR affinity does not exclusively dictate or correlate with diabetogenic potential. Both central and peripheral tolerance mechanisms selectively impinge on the diabetogenic potential of high-affinity TCRs, mitigating their pathogenicity. Thus, TCR affinity and multiple tolerance mechanisms converge to shape and broaden the diabetogenic T cell repertoire, potentially complicating efforts to induce broad, long-term tolerance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.