The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells.
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.
Kaizuka
Yoshihisa
Y
Department of Cellular and Molecular Pharmacology, The Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Douglass
Adam D
AD
Vardhana
Santosh
S
Dustin
Michael L
ML
Vale
Ronald D
RD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D018801:CD2 Antigens / Q000276:immunology*; D018968:CD58 Antigens / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology*; D004357:Drug Synergism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D018801:CD2 Antigens; D018968:CD58 Antigens; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1