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The interaction between a T cell and an antigen-presenting cell (APC) can trigger a signaling response that leads to T cell activation. Prior studies have shown that ligation of the T cell receptor (TCR) triggers a signaling cascade that proceeds through the coalescence of TCR and various signaling molecules (e.g., the kinase Lck and adaptor protein LAT [linker for T cell activation]) into microdomains on the plasma membrane. In this study, we investigated another ligand-receptor interaction (CD58-CD2) that facilities T cell activation using a model system consisting of Jurkat T cells interacting with a planar lipid bilayer that mimics an APC. We show that the binding of CD58 to CD2, in the absence of TCR activation, also induces signaling through the actin-dependent coalescence of signaling molecules (including TCR-zeta chain, Lck, and LAT) into microdomains. When simultaneously activated, TCR and CD2 initially colocalize in small microdomains but then partition into separate zones; this spatial segregation may enable the two receptors to enhance signaling synergistically. Our results show that two structurally distinct receptors both induce a rapid spatial reorganization of molecules in the plasma membrane, suggesting a model for how local increases in the concentration of signaling molecules can trigger T cell signaling.

Original publication

DOI

10.1083/jcb.200809136

Type

Journal article

Journal

J cell biol

Publication Date

04/05/2009

Volume

185

Pages

521 - 534

Keywords

Animals, Antigen-Presenting Cells, Antigens, CD, CD2 Antigens, CD58 Antigens, Cell Adhesion, Cell Membrane, Drug Synergism, Humans, Intercellular Adhesion Molecule-1, Membrane Microdomains, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes