Linker for activation of T cells is displaced from lipid rafts and decreases in lupus T cells after activation via the TCR/CD3 pathway

• Published in: Clinical immunology (Orlando, Fla.) Vol. 142; no. 3; pp. 243 - 251
• Main Authors: Abdoel, Nursamaa, Brun, Susana, Bracho, Carmen, Rodríguez, Martín A, Blasini, Ana M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2012; Elsevier
• Subjects: Adolescent; Adult; Allergy and Immunology; Biological and medical sciences; Child; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunological synapse; Linker for activation of T cells; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lymphocyte Activation; Medical sciences; Membrane microdomains; Membrane Microdomains - immunology; Membrane Microdomains - metabolism; Middle Aged; Phosphorylation; Receptor-CD3 Complex, Antigen, T-Cell - immunology; Receptor-CD3 Complex, Antigen, T-Cell - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Signal Transduction; Systemic lupus erithematosus; T cell signaling; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Young Adult; Immunological synapse; Membrane microdomains; T cell signaling; Systemic lupus erithematosus; Linker for activation of T cells; Immunopathology; Connective tissue disease; Skin disease; Lipid raft; T cell receptor; Autoimmune disease; Activation; Signal transduction; Immunology; Systemic lupus erythematosus; Systemic disease; T-Lymphocyte
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2011.12.010

Abstract Systemic lupus erythematosus (SLE) is characterized by abnormal signal transduction mechanisms in T lymphocytes. Linker for activation of T cells (LAT) couples TCR/CD3 activation with downstream signaling pathways. We reported diminished ERK 1/2 kinase activity in TCR/CD3 stimulated lupus T cells. In this study we evaluated the expression, phosphorylation, lipid raft and immunological synapse (IS) localization and colocalization of LAT with key signalosome molecules. We observed a diminished expression and an abnormal localization of LAT in lipid rafts and at the IS in activated lupus T cells. LAT phosphorylation, capture by GST–Grb2 fusion protein, and coupling to Grb2 and PLCγ1, was similar in healthy control and lupus T cells. Our results suggest that an abnormal localization of LAT within lipid rafts and its accelerated degradation after TCR/CD3 activation may compromise the assembly of the LAT signalosome and downstream signaling pathways required for full MAPK activation in lupus T cells.