ArticleProceedings of the National Academy of Sciences of the United States of America2015
Force-dependent transition in the T-cell receptor β-subunit allosterically regulates peptide discrimination and pMHC bond lifetime.
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 189 papers.
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Who cites it
189 citing papers in PubMed, 256 citations in OpenAlex.
- Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection.Immunity · 2026Article
- Extended local deuteration of leucine enhances methyl NMR of large proteins expressed in eukaryotic cells.Chemical communications (Cambridge, England) · 2026Article
- Predicting specificity of TCR-pMHC interactions using machine-learning and biophysical models.Cell systems · 2026Article
- T cells are blind to the dark mechanics of tumors.Trends open · 2026Review
- Antibody Fc receptor CD16a mediates natural killer cell activation via mechanotransduction of piconewton forces.Science advances · 2026Article
- Engineering a Second Interchain Disulfide Bond in the αβ T-Cell Receptor Constant Domain: A Powerful Strategy to Enhance Stability, Pairing Fidelity, and Therapeutic Efficacy in TCR-T Cell Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Structure-Function Insights into Immune Receptors Drive Innovation in CAR-T Cell Therapy.Current issues in molecular biology · 2026Review
- Overcoming T cell tolerance to tumor self-antigens through catch-bond engineering.Science (New York, N.Y.) · 2026Article
- Mechanical communication and function regulation of immune cells.Fundamental research · 2026Review
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.Frontiers in immunology · 2026Article
- The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.Nature communications · 2025Article
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.bioRxiv : the preprint server for biology · 2025Article
- Atomistic TCR-ligand interactions instruct memory T-cell differentiation.bioRxiv : the preprint server for biology · 2025Article
- Chimeric Antigen Receptors Transmit Co-stimulatory Domain Dependent Piconewton Forces to their Target.bioRxiv : the preprint server for biology · 2025Article
- CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions.Nature communications · 2025Article
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Identifying T cell antigen at the atomic level with graph convolutional network.Nature communications · 2025Article
- FAIR data for optical tweezers experiments.Biophysical journal · 2025Review
- Article
129 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The αβ T-cell receptor (TCR) on each T lymphocyte mediates exquisite specificity for a particular foreign peptide bound to a major histocompatibility complex molecule (pMHC) displayed on the surface of altered cells. This recognition stimulates protection in the mammalian host against intracellular pathogens, including viruses, and involves piconewton forces that accompany pMHC ligation. Physical forces are generated by T-lymphocyte movement during immune surveillance as well as by cytoskeletal rearrangements at the immunological synapse following cessation of cell migration. The mechanistic explanation for how TCRs distinguish between foreign and self-peptides bound to a given MHC molecule is unclear: peptide residues themselves comprise few of the TCR contacts on the pMHC, and pathogen-derived peptides are scant among myriad self-peptides bound to the same MHC class arrayed on infected cells. Using optical tweezers and DNA tether spacer technology that permit piconewton force application and nanometer scale precision, we have determined how bioforces relate to self versus nonself discrimination. Single-molecule analyses involving isolated αβ-heterodimers as well as complete TCR complexes on T lymphocytes reveal that the FG loop in the β-subunit constant domain allosterically controls both the variable domain module's catch bond lifetime and peptide discrimination via force-driven conformational transition. In contrast to integrins, the TCR interrogates its ligand via a strong force-loaded state with release through a weakened, extended state. Our work defines a key element of TCR mechanotransduction, explaining why the FG loop structure evolved for adaptive immunity in αβ but not γδTCRs or immunoglobulins.
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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.