Engagement of GPI-linked CD48 contributes to TCR signals and cytoskeletal reorganization: a role for lipid rafts in T cell activation.
GPI-linked proteins coassociate with intracellular tyrosine kinases in "lipid rafts" proposed to function as platforms for signal transduction and cytoskeletal reorganization. TCR activation requires both tyrosine kinase signals and cytoskeletal reorganization. How receptor engagement initiates cytoskeletal changes remains poorly understood. We investigated the consequences of recruiting GPI-linked CD48 and associated rafts to the site of T cell:APC contact by stimulating T cells with APCs that express the CD48 ligand CD2. We demonstrate that CD2:CD48 interactions enhance TCR-mediated functions. CD48/TCR coengagement qualitatively and quantitatively enhances lipid raft-dependent zeta association with the actin cytoskeleton and zeta tyrosine phosphorylation. This implicates lipid rafts as sites where receptor-induced signals and cytoskeletal reorganization are integrated and reveals a novel component of accessory molecule function.
Moran
M
M
Department of Microbiology, Immunology, and Molecular Genetics, UCLA School of Medicine, Los Angeles, California 90095-1570, USA.
Miceli
M C
MC
D000199:Actins / Q000378:metabolism; D000818:Animals; D000938:Antigen-Presenting Cells; D015703:Antigens, CD / Q000378:metabolism*; D018801:CD2 Antigens / Q000096:biosynthesis; D017252:CD3 Complex / Q000378:metabolism; D000071178:CD48 Antigen; D002458:Cell Fractionation; D003599:Cytoskeleton / Q000378:metabolism / Q000502:physiology; D003902:Detergents; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D007739:L Cells; D050356:Lipid Metabolism; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine
D000199:Actins; D015703:Antigens, CD; D018801:CD2 Antigens; D017252:CD3 Complex; D000071178:CD48 Antigen; C000604066:Cd48 protein, mouse; D003902:Detergents; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D014443:Tyrosine