ArticleImmunology letters2015
TCR and CD28 activate the transcription factor NF-κB in T-cells via distinct adaptor signaling complexes.
Article in Immunology letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 66 citations in OpenAlex.
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- Machine learning-driven discovery of STAT1 and TRIM22 as immune biomarkers for lupus nephritis: translational insights into diagnosis and pathogenesis.Scientific reports · 2026Article
- Proteogenomics Reveals Microproteins in Activated T Cells.Molecular & cellular proteomics : MCP · 2025Article
- Type I Interferon Activates PD-1 Expression through Activation of the STAT1-IRF2 Pathway in Myeloid Cells.Cells · 2024Article
- Mesenchymal stromal cells with chimaeric antigen receptors for enhanced immunosuppression.Nature biomedical engineering · 2024Article
- Inhibition of B cell receptor signaling induced by the human adenovirus species D E3/49K protein.Frontiers in immunology · 2024Article
- A systems and computational biology perspective on advancing CAR therapy.Seminars in cancer biology · 2023Review
- Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.The Journal of experimental medicine · 2023Article
- Toward high-throughput engineering techniques for improving CAR intracellular signaling domains.Frontiers in bioengineering and biotechnology · 2023Article
- Mutations Affecting Genes in the Proximal T-Cell Receptor Signaling Pathway in Peripheral T-Cell Lymphoma.Cancers · 2022Review
- Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium.Stem cell research & therapy · 2022Article
- T-Cell-Specific CerS4 Depletion Prolonged Inflammation and Enhanced Tumor Burden in the AOM/DSS-Induced CAC Model.International journal of molecular sciences · 2022Article
- Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Binding of Staphylococcal Enterotoxin B (SEB) to B7 Receptors Triggers TCR- and CD28-Mediated Inflammatory Signals in the Absence of MHC Class II Molecules.Frontiers in immunology · 2021Article
- The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events.Frontiers in immunology · 2021Review
- Induction of Protective Immunity by a Single Low Dose of a Master Cell Bank cGMP-rBCG-P Vaccine Against the Human Metapneumovirus in Mice.Frontiers in cellular and infection microbiology · 2021Article
- Article
- The Macrophage Responses during Diabetic Oral Ulcer Healing by Liquid Coconut Shell Smoke: An Immunohistochemical Analysis.European journal of dentistry · 2020Article
- Semen exosomes inhibit HIV infection and HIV-induced proinflammatory cytokine production independent of the activation state of primary lymphocytes.FEBS letters · 2020Article
- AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation.The Journal of experimental medicine · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The transcription factor NF-κB is needed for the induction of inflammatory responses in T-cells. Whether its activation by the antigen-receptor and CD28 is mediated by the same or different intracellular signaling pathways has been unclear. Here, using T-cells from various knock-out (Cd28(-/-), adap(-/-)) and knock-in (i.e. Cd28 Y-170F) mice in conjunction with transfected Jurkat T-cells, we show that the TCR and CD28 use distinct pathways to activate NF-κB in T-cells. Anti-CD28 ligation alone activated NF-κB in primary and Jurkat T-cells as measured by NF-κB reporter and EMSA assays. Anti-CD28 also activated NF-κB normally in primary T-cells from adap(-/-) mice, while anti-CD3 stimulation required the adaptor ADAP. Over-expression of ADAP or its binding partner SKAP1 failed to enhance anti-CD28 activation of NF-κB, while ADAP greatly increased anti-CD3 induced NF-κB activity. By contrast, CD28 activation of NF-κB depended on GRB-2 binding to CD28 as seen in CD28 deficient Jurkat T-cells reconstituted with the CD28 YMN-FM mutant, and in primary T-cells from CD28 Y170F mutant knock-in mice. CD28 associated with GRB-2, and GRB-2 siRNA impaired CD28 NF-κB activation. GRB-2 binding partner and guanine nucleotide exchange factor, VAV1, greatly enhanced anti-CD28 driven activation of NF-κB. Further, unlike in the case of anti-CD28, NF-κB activation by anti-CD3 and its cooperation with ADAP was strictly dependent on LAT expression. Overall, we provide evidence that CD28 and the TCR complex regulate NF-κB via different signaling modules of GRB-2/VAV1 and LAT/ADAP pathways respectively.
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