Building the immunological bull's eye

After an antigen-presenting cell meets a T cell, a bull's eye–shaped immunological synapse is formed, with T cell receptors (TCRs) and their antigen clustered in the center, surrounded by a ring of adhesion molecules that holds the cells together. According to Yoshihisa Kaizuka, Adam Douglass, Ronald Vale (University of California, San Francisco, CA), and colleagues, TCRs and adhesion molecules separate early during synapse formation. They might be further segregated by differential interactions with the T cell's actin cytoskeleton.

The movements of the T cell receptor were previously described, but little was known about the movements of adhesion molecules. Direct imaging of T cells in contact with a flat lipid bilayer containing the right ligands showed that TCRs and adhesion molecules initially clustered at the periphery of the contact zone. Each formed their own microdomains in an actin-dependent process. “This early segregation is probably due to different protein–protein interactions that cause these microdomains to coalesce,” Vale says.

The microdomains were then driven inward by retrograde actin flow. The TCRs traveled farther, to the actin-depleted center of the synapse. Adhesion clusters remained in the actin-rich outer portion, unable to travel further inward. They might be stalled by the dense packing of TCRs already in the center or by their own instability in the absence of actin. Neither set traveled as fast as actin itself, probably because they repeatedly slipped off and reattached to the actin conveyor beneath them.

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