Transient μm scale protein accumulation at the center of the T cell antigen presenting cell interface drives efficient IL-2 secretion

A μm scale complex, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen presenting cells. It is of interest as μm scale protein complexes have unique biophysical and signaling properties. To causally determine cSMAC function, we have systematically manipulated the localization of three adaptor proteins, LAT, SLP-76, and Grb2. cSMAC recruitment varied between the adaptors and was consistently diminished upon blockade of the costimulatory receptor CD28 and deficiency of the signal amplifying kinase Itk. Reconstitution of adaptor cSMAC localization by fusion with domains with a strong interface localization preference restored IL-2 secretion as a key T cell effector function as dependent on the precise reconstitution dynamics. Our data establish a model where the cSMAC enhances early signaling by facilitating extensive signaling interactions and attenuates signaling thereafter through sequestration of a more limited set of signaling intermediates.