ArticleThe Journal of clinical investigation2016
Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity.
Article in The Journal of clinical investigation, 2016. 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 89 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.
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
89 citing papers in PubMed, 159 citations in OpenAlex.
- Article
- Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors.Nature biomedical engineering · 2026Article
- Decoding TCR recognition via geometric deep learning of immunological fingerprints.Briefings in bioinformatics · 2026Article
- Murine T-cell receptor OT-I exhibits imperfect discrimination between foreign and self-antigens.The EMBO journal · 2026Article
- HLA class I-specific nucleolin peptides induce therapeutic T cells in triple-negative breast cancer patients.International journal of biological sciences · 2026Article
- THLANet: A deep learning framework for predicting TCR-pHLA binding in immunotherapy applications.PLoS computational biology · 2025Article
- TCR catch bonds nonlinearly control CD8 cooperation to shape T cell specificity.Cell research · 2025Article
- Single-cell analysis reveals islet autoantigen's immune activation in type 1 diabetes patients.Journal of clinical biochemistry and nutrition · 2025Article
- IL17-deficient NOD mice are protected from autoimmune diabetes due to decreased antigen presentation and T cell activation.Frontiers in immunology · 2025Article
- Linking epigenetic mechanisms of T cell dysfunction with pathophysiology of type 1 diabetes mellitus.Frontiers in immunology · 2025Review
- The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.Immunological reviews · 2025Review
- Unveiling cross-reactivity: implications for immune response modulation in cancer.Briefings in bioinformatics · 2024Article
- Broadening alloselectivity of T cell receptors by structure guided engineering.Scientific reports · 2024Article
- Dataset from a human-in-the-loop approach to identify functionally important protein residues from literature.Scientific data · 2024Article
- Mesothelin- and nucleolin-specific T cells from combined short peptides effectively kill triple-negative breast cancer cells.BMC medicine · 2024Article
- HLA A*24:02-restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes.The Journal of clinical investigation · 2024Article
- Engineering Probiotics for Diabetes Management: Advances, Challenges, and Future Directions in Translational Microbiology.International journal of nanomedicine · 2024Review
- Article
- HLA3DB: comprehensive annotation of peptide/HLA complexes enables blind structure prediction of T cell epitopes.Nature communications · 2023Article
- Defining and Studying B Cell Receptor and TCR Interactions.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development of autoimmunity. However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide-major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I-restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides. We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide. Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and-key-like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot. Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand. Together, these data highlight how T cell cross-reactivity with pathogen-derived antigens might break self-tolerance to induce autoimmune disease.
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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.