ArticleThe Journal of biological chemistry2016
Pre-T Cell Receptors (Pre-TCRs) Leverage Vβ Complementarity Determining Regions (CDRs) and Hydrophobic Patch in Mechanosensing Thymic Self-ligands.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 80 citations in OpenAlex.
- Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection.Immunity · 2026Article
- Article
- 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
- Probing the Dynamic Strength of Biomolecular Interactions with Single-Cell Centrifugation.ACS central science · 2025Article
- CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions.Nature communications · 2025Article
- High-Throughput Centrifuge Force Microscopy Reveals Dynamic Immune-Cell Avidity at the Single-Cell Level.bioRxiv : the preprint server for biology · 2025Article
- Biophysical and Structural Features of αβT-Cell Receptor Mechanosensing: A Paradigmatic Shift in Understanding T-Cell Activation.Immunological reviews · 2025Review
- Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
- Mechanotransduction governs CD40 function and underlies X-linked hyper-IgM syndrome.Science advances · 2024Article
- Mechanical force matters in early T cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Parsing digital or analog TCR performance through piconewton forces.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
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- Article
- The self-reactive FVIII T cell repertoire in healthy individuals relies on a short set of epitopes and public clonotypes.Frontiers in immunology · 2024Article
- A Mechanical Assay for the Quantification of Anti-RBD IgG Levels in Finger-Prick Whole Blood.ACS sensors · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The pre-T cell receptor (pre-TCR) is a pTα-β heterodimer functioning in early αβ T cell development. Although once thought to be ligand-autonomous, recent studies show that pre-TCRs participate in thymic repertoire formation through recognition of peptides bound to major histocompatibility molecules (pMHC). Using optical tweezers, we probe pre-TCR bonding with pMHC at the single molecule level. Like the αβTCR, the pre-TCR is a mechanosensor undergoing force-based structural transitions that dynamically enhance bond lifetimes and exploiting allosteric control regulated via the Cβ FG loop region. The pre-TCR structural transitions exhibit greater reversibility than TCRαβ and ordered force-bond lifetime curves. Higher piconewton force requires binding through both complementarity determining region loops and hydrophobic Vβ patch apposition. This patch functions in the pre-TCR as a surrogate Vα domain, fostering ligand promiscuity to favor development of β chains with self-reactivity but is occluded by α subunit replacement of pTα upon αβTCR formation. At the double negative 3 thymocyte stage where the pre-TCR is first expressed, pre-TCR interaction with self-pMHC ligands imparts growth and survival advantages as revealed in thymic stromal cultures, imprinting fundamental self-reactivity in the T cell repertoire. Collectively, our data imply the existence of sequential mechanosensor αβTCR repertoire tuning via the pre-TCR.
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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.