ArticleNature immunology2015
T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex.
Article in Nature immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 136 citations in OpenAlex.
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- Trogocytosis-derived regulatory cluster of differentiation 8-positive T cells facilitate induction of immune tolerance after lung transplantation.JTCVS open · 2026Article
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- Tailoring monocyte-derived tolerogenic cell therapies to the needs; what's in a name?Molecular therapy. Methods & clinical development · 2025Article
- STCRpy: a software suite for T-cell receptor structure parsing, interaction profiling, and machine learning dataset preparation.Bioinformatics (Oxford, England) · 2025Article
- A general system for targeting MHC class II-antigen complex via a single adaptable loop.Nature biotechnology · 2025Article
- A naturally selected αβ T cell receptor binds HLA-DQ2 molecules without co-contacting the presented peptide.Nature communications · 2025Article
- The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.Immunological reviews · 2025Review
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
- Unveiling cross-reactivity: implications for immune response modulation in cancer.Briefings in bioinformatics · 2024Article
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- Oral Insulin Delay of Stage 3 Type 1 Diabetes Revisited in HLA DR4-DQ8 Participants in the TrialNet Oral Insulin Prevention Trial (TN07).Diabetes care · 2024Article
- The Evolving Portrait of γδ TCR Recognition Determinants.Journal of immunology (Baltimore, Md. : 1950) · 2024Review
- Defining Human Regulatory T Cells beyond FOXP3: The Need to Combine Phenotype with Function.Cells · 2024Review
- Can AlphaFold's breakthrough in protein structure help decode the fundamental principles of adaptive cellular immunity?Nature methods · 2024Review
- Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes.Science advances · 2023Article
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37 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 5 institutions in 4 countries.
Funding
Abstract
Central to adaptive immunity is the interaction between the αβ T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iT(reg)) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 180° polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iT(reg) TCR α-chain and β-chain are overlaid with the α-chain and β-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition.
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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.