ArticleNature immunology2022
Kinetic proofreading through the multi-step activation of the ZAP70 kinase underlies early T cell ligand discrimination.
Article in Nature immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 57 citations in OpenAlex.
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- Antibody Fc receptor CD16a mediates natural killer cell activation via mechanotransduction of piconewton forces.Science advances · 2026Article
- Manufacturing synthetic viscoelastic antigen-presenting cells for immunotherapy.Nature protocols · 2026Review
- Identification and validation of ZAP70 as a potential biomarker associated with T cell infiltration in lung adenocarcinoma.Translational cancer research · 2026Article
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Antibody Fc receptor CD16a mediates natural killer cell activation via mechanotransduction of piconewton forces.bioRxiv : the preprint server for biology · 2026Article
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Multidimensional mapping of stimulation-responsive regulatory elements and candidate causal variants in T cell activation.Science advances · 2026Article
- A comparative mathematical modeling study of phenotypic approaches to T cell activation.Scientific reports · 2025Article
- Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire.Nature immunology · 2025Article
- Parallel reactions on a single T cell receptor offer a robust kinetic proofreading mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Discordant CAR-T cell signaling: implications of divergence from physiological T cell activation.Journal of translational medicine · 2025Review
- Remote Force Modulation of the T-Cell Receptor Reveals an NFAT-Threshold for CD4European journal of immunology · 2025Article
- Histocompatibility in Botryllus schlosseri and the origins of adaptive immunity.Immunogenetics · 2025Review
- QRICH1 mediates an intracellular checkpoint for CD8Science immunology · 2025Article
- CD28 is superior to 4-1BB costimulation in generating CAR-NK cells for tumor immunotherapy.Experimental hematology & oncology · 2025Article
- Low-avidity T cells drive endogenous tumor immunity in mice and humans.Nature immunology · 2025Article
- Roles of TULA-family proteins in T cells and autoimmune diseases.Genes and immunity · 2025Review
- CD6 regulates CD4 T follicular helper cell differentiation and humoral immunity during murine coronavirus infection.Journal of virology · 2025Article
- The CD38Frontiers in immunology · 2025Article
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11 authors at 2 institutions in 2 countries.
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Abstract
T cells recognize a few high-affinity antigens among a vast array of lower affinity antigens. According to the kinetic proofreading model, antigen discrimination properties could be explained by the gradual amplification of small differences in binding affinities as the signal is transduced downstream of the T cell receptor. Which early molecular events are affected by ligand affinity, and how, has not been fully resolved. Here, we used time-resolved high-throughput proteomic analyses to identify and quantify the phosphorylation events and protein-protein interactions encoding T cell ligand discrimination in antigen-experienced T cells. Although low-affinity ligands induced phosphorylation of the Cd3 chains of the T cell receptor and the interaction of Cd3 with the Zap70 kinase as strongly as high-affinity ligands, they failed to activate Zap70 to the same extent. As a result, formation of the signalosome of the Lat adaptor was severely impaired with low- compared with high-affinity ligands, whereas formation of the signalosome of the Cd6 receptor was affected only partially. Overall, this study provides a comprehensive map of molecular events associated with T cell ligand discrimination.
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