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The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells

¹ The Howard Hughes Medical Institute and ² Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143
³ Program in Molecular Pathogenesis, Helen and Martin Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Pathology, New York University School of Medicine, New York, NY 10016

Correspondence to Ronald D. Vale: vale{at}cmp.ucsf.edu

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- 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.

© 2009 Kaizuka et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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This article has been cited by other articles:

• Kaizuka, Y., Douglass, A. D., Vardhana, S., Dustin, M. L., Vale, R. D. (2009). The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells. JEM 206: i9-i9 [Full Text]  
• Williams, R. (2009). How T cells shape their signals. JCB 185: 372-372 [Full Text]  

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