A simple twist of phosphate: Immunological synapse formation and T cell receptor signaling outcome in regulatory T cells

Signaling through the T cell receptor (TCR) regulates T cell homeostasis and effector func-tions. However, a full accounting of the TCR-coupled signaling networks and how theirinterplay determines specific functional outcomes remains elusive. Of particular interestare efforts over the last years to elucidate distinctive features of TCR signaling in regu-latory T cells (Treg) that may account for some of their unique functional attributes ascompared to conventional T (Tconv) cells. In this issue of the European Journal of Immunol-ogy, van Ham et al. [Eur. J. Immunol. 2017. 47: 2043–2058] employed differential phos-phoproteomics to identify a set of 11 proteins mainly linked to cytoskeletal organizationand molecular transport that discriminate between TCR signaling in the respective cellsubset. They further linked these differences to cell subset-specific alterations in thespatio-temporal organization of signaling pathways at immune synapse (IS) in Treg ver-sus T conv. These data support the idea that these proteins may act as a molecular“twist” element driving Treg cell-specific responses by affecting cytoskeletal dynamicsand IS formation. Taken together, these findings may facilitate the development of novelimmunomodulatory agents that exploit differences in TCR signaling between Treg andTconv cell