Abstract
The formation of supramolecular activation clusters within the immunological synapse, crucial for sustained signaling and T lymphocyte activation, requires costimulation-dependent reorganization of the actin cytoskeleton. Here we have identified the actin-remodeling protein cofilin as a key player in this process. Cell-permeable peptides that block costimulation-induced cofilin/F-actin interactions in untransformed human T lymphocytes impair receptor capping and immunological synapse formation at the interface between T cells and antigen-presenting cells. As a consequence, T cell activation, as measured by cytokine production and proliferation, is inhibited.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Depolymerizing Factors
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Actins / antagonists & inhibitors
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Actins / metabolism
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Antigen-Presenting Cells / drug effects
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Antigen-Presenting Cells / immunology
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CD2 Antigens / immunology
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CD2 Antigens / metabolism
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Carrier Proteins / metabolism
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Cell Division / drug effects
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Cell Line, Tumor
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Cell Membrane Permeability
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Cell-Penetrating Peptides
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Cells, Cultured
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Cytokines / biosynthesis
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Cytokines / immunology
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Humans
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Immunologic Capping / drug effects
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Isoantigens / immunology
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Lymphocyte Activation / drug effects*
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Microfilament Proteins / chemistry*
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Peptides / chemistry
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Peptides / metabolism
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Peptides / pharmacology*
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Protein Binding / drug effects
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T-Lymphocytes / drug effects*
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T-Lymphocytes / immunology*
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Th1 Cells / drug effects
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Th1 Cells / immunology
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Th2 Cells / drug effects
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Th2 Cells / immunology
Substances
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Actin Depolymerizing Factors
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Actins
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CD2 Antigens
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Carrier Proteins
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Cell-Penetrating Peptides
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Cytokines
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Isoantigens
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Microfilament Proteins
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Peptides
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penetratin