Published online
doi:10.1083/jcb.1853iti3
The Journal of Cell Biology, Vol. 185, No. 3, 372-
The Rockefeller University Press, 0021-9525 $30.00
© Williams
How T cells shape their signals
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TCR (blue) and CD2 (green) form a bullseye and ring arrangement when they cluster at the T cell surface.
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Kaizuka et al. describe the shape of signaling during T cell activation.
When antigen- presenting cells (APCs) and T cells get together, the two become locked in a synaptic embrace that triggers T cell activation. The synapse centers around antigen recognition by the T cell receptor (TCR), but other proteins on the cells surfaces also partake in the union. One such pair of proteins is CD58 and CD2, which reside on the APC and T cell, respectively. Whether the coupling of this pair simply increases adhesion between the cells or also triggers a signaling cascade has been a point of debate.
Kaizuka et al. have now gotten to the bottom of the matter by observing the CD58–CD2 interaction independently of other cell–cell interactions. Planar lipid bilayers, which mimic the APC's membrane but contain just one or two proteins of interest, were prepared on microscope coverslips. The team then followed the reactions of T cells to the bilayers, both visually and biochemically.
When presented with CD58, the CD2 receptors on the T cell's surface came together into small clusters. When presented with both CD58 and anti-TCR antibody, CD2 and TCR initially coalesced for several minutes, and then rearranged so that TCR formed a central bullseye surrounded by a ring of CD2.
As for signaling, CD58 or anti-TCR alone triggered the same initial kinase cascade in the T cell. But when presented together, the activation of these kinases was more robust, suggesting synergy. Active kinases were also clustered at the T cell's cortex reflecting the receptor clustering on the cell surface, and interestingly, when CD2 and TCR formed their bullseye and ring arrangement, the kinases were most abundant in the ring. As yet, however, the significance of these signal shapes remains to be determined.
References
Kaizuka, Y., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200809136.[Abstract/Free Full Text]
Ruth Williams
ruth.williams{at}rockefeller.edu

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