Synaptic synergy of T cell receptor and interleukin 2 receptor in CD8⁺T cells

Interleukin 2 (IL2) promotes T cell proliferation and differentiation, making it a central target in immunotherapies. T cells fine-tune their sensitivity to and consumption of IL2 by regulating surface expression and composition of the IL2 receptor. Following antigen recognition, IL2 receptor signaling is shared through polarized interactions in T cell aggregates. However, how IL2 function is integrated during earlier antigen-dependent T cell synapses is unknown. Here, we demonstrate a synergistic effect between the T cell receptor (TCR) and IL2 receptor signaling at the immunological synapse of CD8 + T cells with supported lipid bilayers. TCR and IL2 signaling overlapped in space and time, potentiating each other when simultaneously triggered. Immuno-STATs, a safe and effective new class of immunotherapeutics, which fuse IL2 and peptide-major histocompatibility complex (pMHC) in a single molecule to expand antigen-specific CD8 + T cells, enhanced both TCR and IL2 signaling and promoted antigen specific T-T immunological synapses.