ArticleProceedings of the National Academy of Sciences of the United States of America2002
CD28 plays a critical role in the segregation of PKC theta within the immunologic synapse.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 140 citations in OpenAlex.
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- Immunotherapy of cancer without induction of autoimmunity - CD6 as a therapeutic target.Frontiers in immunology · 2026Review
- How persistent infection overcomes peripheral tolerance mechanisms to cause T cell-mediated autoimmune disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
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- Fifteen Years of Sm-p80-Based Vaccine Trials in Nonhuman Primates: Antibodies From Vaccinated Baboons Confer ProtectionFrontiers in immunology · 2020Article
- Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease.Stem cell research · 2019Article
- ISGylation - a key to lock the cell gates for preventing the spread of threats.Journal of cell science · 2017Review
- eNOS S-nitrosylates β-actin on Cys374 and regulates PKC-θ at the immune synapse by impairing actin binding to profilin-1.PLoS biology · 2017Article
- Microtubule-associated protein-4 controls nanovesicle dynamics and T cell activation.Journal of cell science · 2017Article
- PKCθ links proximal T cell and Notch signaling through localized regulation of the actin cytoskeleton.eLife · 2017Article
- CD28 Costimulation: From Mechanism to Therapy.Immunity · 2016Review
- Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition.Frontiers in immunology · 2016Review
- Review
- TCR-induced sumoylation of the kinase PKC-θ controls T cell synapse organization and T cell activation.Nature immunology · 2015Article
- Troxis necrosis, a novel mechanism for drug-induced hepatitis secondary to immunomodulatory therapy.Experimental and molecular pathology · 2015Article
- The Novel PKCθ from Benchtop to Clinic.Journal of immunology research · 2015Review
- The Role of PKC-θ in CD4+ T Cells and HIV Infection: To the Nucleus and Back Again.Frontiers in immunology · 2015Review
- The bullseye synapse formed between CD4+ T-cell and staphylococcal enterotoxin B-pulsed dendritic cell is a suppressive synapse in T-cell response.Immunology and cell biology · 2015Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The signaling pathways that lead to the localization of cellular protein to the area of interaction between T cell and antigen-presenting cell and the mechanism by which these molecules are further sorted to the peripheral supramolecular activation cluster or central supramolecular activation cluster regions of the immunologic synapse are poorly understood. In this study, we investigated the functional involvement of CD28 costimulation in the T cell receptor (TCR)-mediated immunologic synapse formation with respect to protein kinase C (PKC)theta; localization. We showed that CD3 crosslinking alone was sufficient to induce PKC theta; capping in naive CD4(+) T cells. Studies with pharmacologic inhibitors and knockout mice showed that the TCR-derived signaling that drives PKC theta; membrane translocation requires the Src family kinase, Lck, but not Fyn. In addition, a time course study of the persistence of T cell molecules to the immunologic synapse indicated that PKC theta;, unlike TCR, persisted in the synapse for at least 4 h, a time that is sufficient for commitment of a T cell to cell division. Finally, by using TCR-transgenic T cells from either wild-type or CD28-deficient mice, we showed that CD28 expression was required for the formation of the mature immunologic synapse, because antigen stimulation of CD28(-) T cells led to a diffuse pattern of localization of PKC theta; and lymphocyte function-associated antigen-1 in the immunologic synapse, in contrast to the central supramolecular activation cluster localization of PKC theta; in CD28(+) T cells.
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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.