Dynamics of the immunological synapse: finding, establishing and solidifying a connection.

A coordinated series of molecular interactions leads to the establishment of an immunological synapse. Migrating lymphocytes scan antigen-processing cells and are made to stop upon recognition of their specific ligand. Microclusters of TCRs/CD4 form over a large contact site, then TCRs coalesce. Coalescence occurs in response to signals generated in the first encounters and in response to costimulatory signaling. The cytoskeleton rearranges and concentric rings of coreceptors and integrins surround the TCRs. This unexpected level of complexity of co-clustering and exclusion in the interface has generated much interest in the functional consequences of signaling and/or immune effector function.