EWI-2 association with α-actinin regulates T cell immune synapses and HIV viral infection

• Published in: The Journal of immunology (1950) 2012-07, Vol.189 (2), p.689-700
• Main Authors: Gordón-Alonso, Mónica, Sala-Valdés, Mónica, Rocha-Perugini, Vera, Pérez-Hernández, Daniel, López-Martín, Soraya, Ursa, Angeles, Alvarez, Susana, Kolesnikova, Tatiana V, Vázquez, Jesús, Sánchez-Madrid, Francisco, Yáñez-Mó, María
• Format: Article
• Language: English
• Subjects: Actinin - metabolism; Actinin - physiology; Amino Acid Sequence; Antigen Presentation - immunology; Antigens, CD - metabolism; Antigens, CD - physiology; Cell Line, Transformed; Cytoskeleton - immunology; Cytoskeleton - pathology; Cytoskeleton - virology; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - pathology; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immunological Synapses - metabolism; Immunological Synapses - pathology; Immunological Synapses - virology; Jurkat Cells; Lymphocyte Activation - immunology; Membrane Microdomains - immunology; Membrane Microdomains - pathology; Membrane Microdomains - virology; Membrane Proteins - metabolism; Membrane Proteins - physiology; Molecular Sequence Data; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - pathology; T-Lymphocyte Subsets - virology; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1103708

EWI motif-containing protein 2 (EWI-2) is a member of the Ig superfamily that links tetraspanin-enriched microdomains to the actin cytoskeleton. We found that EWI-2 colocalizes with CD3 and CD81 at the central supramolecular activation cluster of the T cell immune synapse. Silencing of the endogenous expression or overexpression of a cytoplasmic truncated mutant of EWI-2 in T cells increases IL-2 secretion upon Ag stimulation. Mass spectrometry experiments of pull-downs with the C-term intracellular domain of EWI-2 revealed the specific association of EWI-2 with the actin-binding protein α-actinin; this association was regulated by PIP2. α-Actinin regulates the immune synapse formation and is required for efficient T cell activation. We extended these observations to virological synapses induced by HIV and found that silencing of either EWI-2 or α-actinin-4 increased cell infectivity. Our data suggest that the EWI-2-α-actinin complex is involved in the regulation of the actin cytoskeleton at T cell immune and virological synapses, providing a link between membrane microdomains and the formation of polarized membrane structures involved in T cell recognition.