ArticleProceedings of the National Academy of Sciences of the United States of America2015
Pre-TCR ligand binding impacts thymocyte development before αβTCR expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 76 citations in OpenAlex.
- LB-PaCS-MD Guided Simulations Reveal Transient Stabilization during TCR-pMHC Dissociation.Journal of chemical information and modeling · 2026Article
- Mechanoimmunology: past, present, and future perspectives.Mechanobiology in medicine · 2026Review
- Atomistic TCR-ligand interactions instruct memory T-cell differentiation.bioRxiv : the preprint server for biology · 2025Article
- CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions.Nature communications · 2025Article
- Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Biophysical and Structural Features of αβT-Cell Receptor Mechanosensing: A Paradigmatic Shift in Understanding T-Cell Activation.Immunological reviews · 2025Review
- Mechanotransduction governs CD40 function and underlies X-linked hyper-IgM syndrome.Science advances · 2024Article
- Efficient and economic protein labeling for NMR in mammalian expression systems: Application to a preT-cell and T-cell receptor protein.Protein science : a publication of the Protein Society · 2024Article
- Mechanical forces amplify TCR mechanotransduction in T cell activation and function.Applied physics reviews · 2024Review
- Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry.Blood cancer journal · 2024Article
- The self-reactive FVIII T cell repertoire in healthy individuals relies on a short set of epitopes and public clonotypes.Frontiers in immunology · 2024Article
- Pre-T cell receptor localization and trafficking are independent of its signaling.The Journal of cell biology · 2023Article
- Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology.Proceedings of the National Academy of Sciences of the United States of America · 2023Review
- Catch bond models may explain how force amplifies TCR signaling and antigen discrimination.Nature communications · 2023Article
- E-cadherin in developing murine T cells controls spindle alignment and progression through β-selection.Science advances · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- The β-selection step shapes T-cell identity.Nature · 2023Article
- Stepwise progression of β-selection during T cell development involves histone deacetylation.Life science alliance · 2023Article
- Mechanosurveillance: Tiptoeing T Cells.Frontiers in immunology · 2022Review
- Molecular design of the γδT cell receptor ectodomain encodes biologically fit ligand recognition in the absence of mechanosensing.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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13 authors at 3 institutions in 1 country.
Funding
Abstract
Adaptive cellular immunity requires accurate self- vs. nonself-discrimination to protect against infections and tumorous transformations while at the same time excluding autoimmunity. This vital capability is programmed in the thymus through selection of αβT-cell receptors (αβTCRs) recognizing peptides bound to MHC molecules (pMHC). Here, we show that the pre-TCR (preTCR), a pTα-β heterodimer appearing before αβTCR expression, directs a previously unappreciated initial phase of repertoire selection. Contrasting with the ligand-independent model of preTCR function, we reveal through NMR and bioforce-probe analyses that the β-subunit binds pMHC using Vβ complementarity-determining regions as well as an exposed hydrophobic Vβ patch characteristic of the preTCR. Force-regulated single bonds akin to those of αβTCRs but with more promiscuous ligand specificity trigger calcium flux. Thus, thymic development involves sequential β- and then, αβ-repertoire tuning, whereby preTCR interactions with self pMHC modulate early thymocyte expansion, with implications for β-selection, immunodominant peptide recognition, and germ line-encoded MHC interaction.
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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.