Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

The Journal of Cell Biology

Publication Date

05/2009

Volume

185

Pages

521 - 534

Addresses

Department of Cellular and Molecular Pharmacology, The Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA.

Keywords

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