ArticleJCI insight2021
Autoreactive T cell receptors with shared germline-like α chains in type 1 diabetes.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Research progress on the application of single-cell sequencing in autoimmune diseases.Genes and immunity · 2023Pooled it
- Article
- Mitochondrial dysfunction in type 1 diabetes and its implications for pancreatic beta-cell survival and insulin secretion.Acta diabetologica · 2026Review
- Deciphering antigen-driven T cell responses through vectorized TCRdist sequence neighborhood quantification.bioRxiv : the preprint server for biology · 2026Article
- Quantitative V gene-targeted T cell receptor sequencing as a biomarker in type 1 diabetes.JCI insight · 2026Article
- Decoding autoimmune disease with single-cell immune repertoire and transcriptome sequencing: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Current trends in single-cell RNA sequencing applications in diabetes mellitus.FEBS open bio · 2025Review
- Activated polyreactive B cells are clonally expanded in autoantibody positive and patients with recent-onset type 1 diabetes.Cell reports · 2025Article
- Deciphering Autoimmune Diseases: Unveiling the Diagnostic, Therapeutic, and Prognostic Potential of Immune Repertoire Sequencing.Inflammation · 2025Review
- Disease diagnostics using machine learning of B cell and T cell receptor sequences.Science (New York, N.Y.) · 2025Article
- Antigen-specific immunotherapies for autoimmune disease.Nature reviews. Rheumatology · 2025Review
- Article
- Integrating Omics into Functional Biomarkers of Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Islet-antigen reactive B cells display a unique phenotype and BCR repertoire in autoantibody positive and recent-onset type 1 diabetes patients.bioRxiv : the preprint server for biology · 2024Article
- Germline-like TCR-α chains shared between autoreactive T cells in blood and pancreas.Nature communications · 2024Article
- Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection.Frontiers in endocrinology · 2024Review
- A minority of proliferating human CD4Frontiers in immunology · 2024Article
- Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes.Science advances · 2023Article
- Translational immunology: Applying fundamental discoveries to human health and autoimmune diseases.European journal of immunology · 2023Review
- Islet-autoreactive CD4+ T cells are linked with response to alefacept in type 1 diabetes.JCI insight · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Human islet antigen reactive CD4+ memory T cells (IAR T cells) play a key role in the pathogenesis of autoimmune type 1 diabetes (T1D). Using single-cell RNA sequencing (scRNA-Seq) to identify T cell receptors (TCRs) in IAR T cells, we have identified a class of TCRs that share TCRα chains between individuals ("public" chains). We isolated IAR T cells from blood of healthy, new-onset T1D and established T1D donors using multiplexed CD154 enrichment and identified paired TCRαβ sequences from 2767 individual cells. More than a quarter of cells shared TCR junctions between 2 or more cells ("expanded"), and 29/47 (~62%) of expanded TCRs tested showed specificity for islet antigen epitopes. Public TCRs sharing TCRα junctions were most prominent in new-onset T1D. Public TCR sequences were more germline like than expanded unique, or "private," TCRs, and had shorter junction sequences, suggestive of fewer random nucleotide insertions. Public TCRα junctions were often paired with mismatched TCRβ junctions in TCRs; remarkably, a subset of these TCRs exhibited cross-reactivity toward distinct islet antigen peptides. Our findings demonstrate a prevalent population of IAR T cells with diverse specificities determined by TCRs with restricted TCRα junctions and germline-constrained antigen recognition properties. Since these "innate-like" TCRs differ from previously described immunodominant TCRβ chains in autoimmunity, they have implications for fundamental studies of disease mechanisms. Self-reactive restricted TCRα chains and their associated epitopes should be considered in fundamental and translational investigations of TCRs in T1D.
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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.