Kupfer‐type immunological synapses in vivo : Raison D’être of SMAC

T cells engage with antigen‐presenting cells to form immunological synapses. These intimate contacts are characterized by the complex arrangement of molecules at the intercellular interface, which has been described as the supramolecular activation cluster (SMAC). However, due to T cells functioning without SMAC formation and the difficulties of studying these complex arrangements in vivo, its biological importance has been questioned. In light of recent data, we focus this review on the putative functionality of SMACs in T‐cell synaptic contacts in vivo and emphasize the therapeutic potential of SMAC manipulation in immune‐driven diseases.