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

Capera, J.; Jainarayanan, A. K.; Valvo, S.; Chen, L.; Quayle, S. N.; Moniz, R. J.; Suri, A.; Dustin, M.

doi:10.1101/2024.08.13.607831

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bioRxiv · 10.1101/2024.08.13.607831

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

Capera, J.·Jainarayanan, A. K.·Valvo, S.·Chen, L.·Quayle, S. N.·Moniz, R. J.·Suri, A.·Dustin, M.

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Abstract

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.

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Capera, J., Jainarayanan, A. K., Valvo, S., Chen, L., Quayle, S. N., Moniz, R. J., Suri, A., Dustin, M.. 2024-08-15. Synaptic synergy of T cell receptor and interleukin 2 receptor in CD8+ T cells. https://doi.org/10.1101/2024.08.13.607831

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