ArticleThe Journal of experimental medicine2002
Surface cytotoxic T lymphocyte-associated antigen 4 partitions within lipid rafts and relocates to the immunological synapse under conditions of inhibition of T cell activation.
Article in The Journal of experimental medicine, 2002. 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, 106 citations in OpenAlex.
- Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients.Proceedings of the National Academy of Sciences of the United States of America · 2003Trial
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- Unraveling Immune Checkpoint Inhibitor-Associated Cardiovascular Toxicities: Pathway Insights, Mechanisms, and Emerging Therapeutic Targets.Reviews in cardiovascular medicine · 2026Review
- Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.Science advances · 2025Article
- Recent highlights in the immunomodulatory aspects of Treg cell-derived extracellular vesicles: special emphasis on autoimmune diseases and transplantation.Cell & bioscience · 2022Review
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
- MHC class II molecules on pancreatic cancer cells indicate a potential for neo-antigen-based immunotherapy.Oncoimmunology · 2022Article
- Role of endocytosis and trans-endocytosis in ICOS costimulator-induced downmodulation of the ICOS Ligand.Journal of leukocyte biology · 2021Article
- Article
- A guide to cancer immunotherapy: from T cell basic science to clinical practice.Nature reviews. Immunology · 2020Review
- Development of immune checkpoint therapy for cancer.The Journal of experimental medicine · 2019Review
- Checkpoint inhibitors in hematological malignancies.Journal of hematology & oncology · 2017Review
- Review
- Confusing signals: recent progress in CTLA-4 biology.Trends in immunology · 2015Review
- Diverse mechanisms regulate the surface expression of immunotherapeutic target ctla-4.Frontiers in immunology · 2014Review
- PAG/Cbp suppression reveals a contribution of CTLA-4 to setting the activation threshold in T cells.Cell communication and signaling : CCS · 2013Article
- Article
- Ligation of cytotoxic T lymphocyte antigen-4 to T cell receptor inhibits T cell activation and directs differentiation into Foxp3+ regulatory T cells.The Journal of biological chemistry · 2012Article
- Mitochondrial and plasma membrane pools of stomatin-like protein 2 coalesce at the immunological synapse during T cell activation.PloS one · 2012Article
- The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses.Nature reviews. Immunology · 2011Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell activation through the T cell receptor (TCR) involves partitioning of receptors into discrete membrane compartments known as lipid rafts, and the formation of an immunological synapse (IS) between the T cell and antigen-presenting cell (APC). Compartmentalization of negative regulators of T cell activation such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is unknown. Recent crystal structures of B7-ligated CTLA-4 suggest that it may form lattices within the IS which could explain the mechanism of action of this molecule. Here, we show that after T cell stimulation, CTLA-4 coclusters with the TCR and the lipid raft ganglioside GM1 within the IS. Using subcellular fractionation, we show that most lipid raft-associated CTLA-4 is on the T cell surface. Such compartmentalization is dependent on the cytoplasmic tail of CTLA-4 and can be forced with a glycosylphosphatidylinositol-anchor in CTLA-4. The level of CTLA-4 within lipid rafts increases under conditions of APC-dependent TCR-CTLA-4 coligation and T cell inactivation. However, raft localization, although necessary for inhibition of T cell activation, is not sufficient for CTLA-4-mediated negative signaling. These data demonstrate that CTLA-4 within lipid rafts migrates to the IS where it can potentially form lattice structures and inhibit T cell activation.
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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.