ArticleImmunity, inflammation and disease2021
Separate signaling events control TCR downregulation and T cell activation in primary human T cells.
Article in Immunity, inflammation and disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Article
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- Composition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis.Science advances · 2025Article
- Telomerase RNA component knockout exacerbateseLife · 2024Article
- Spatiotemporal control of immune responses with nucleic acid cocktail vaccine.Advanced therapeutics · 2024Article
- Parsing digital or analog TCR performance through piconewton forces.Science advances · 2024Article
- The quantum model of T-cell activation: Revisiting immune response theories.Scandinavian journal of immunology · 2024Article
- CD3 downregulation identifies high-avidity, multipotent SARS-CoV-2 vaccine- and recall antigen-specific Th cells with distinct metabolism.JCI insight · 2024Article
- CD3ε of a pan T cell marker involved in mouseInternational journal of ophthalmology · 2024Article
- Ectopic ATP synthase stimulates the secretion of extracellular vesicles in cancer cells.Communications biology · 2023Article
- Soluble factors from TLR4- or TCR-activated cells contribute to stability of the resting phenotype and increase the expression of CXCR4 of human memory CD4 T cells.Immunologic research · 2023Article
- An optimized retroviral toolbox for overexpression and genetic perturbation of primary lymphocytes.Biology open · 2022Article
- T cell receptor (TCR) signaling in health and disease.Signal transduction and targeted therapy · 2021Review
- Separate signaling events control TCR downregulation and T cell activation in primary human T cells.Immunity, inflammation and disease · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
introductionT-cell antigen receptor (TCR) interaction with cognate peptide:MHC complexes trigger clustering of TCR:CD3 complexes and signal transduction. Triggered TCR:CD3 complexes are rapidly internalized and degraded in a process called ligand-induced TCR downregulation. Classic studies in immortalized T-cell lines have revealed a major role for the Src family kinase Lck in TCR downregulation. However, to what extent a similar mechanism operates in primary human T cells remains unclear.
methodsHere, we developed an anti-CD3-mediated TCR downregulation assay, in which T-cell gene expression in primary human T cells can be knocked down by microRNA constructs. In parallel, we used CRISPR/Cas9-mediated knockout in Jurkat cells for validation experiments.
resultsWe efficiently knocked down the expression of tyrosine kinases Lck, Fyn, and ZAP70, and found that, whereas this impaired T cell activation and effector function, TCR downregulation was not affected. Although TCR downregulation was marginally inhibited by the simultaneous knockdown of Lck and Fyn, its full abrogation required broad-acting tyrosine kinase inhibitors.
conclusionsThese data suggest that there is substantial redundancy in the contribution of individual tyrosine kinases to TCR downregulation in primary human T cells. Our results highlight that TCR downregulation and T cell activation are controlled by different signaling events and illustrate the need for further research to untangle these processes.
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