Spatiotemporal co-regulation of IL2 and TCR receptors reveals early antigen-driven synaptic synergy in human CD8+ T cells
Abstract
Interleukin 2 (IL2) promotes T cell proliferation and differentiation, making it a central target in immunotherapies. Following antigen recognition, IL2 receptor (IL2R) signaling polarizes towards the immunological synapse (IS). However, how IL2 function is integrated during earlier antigen-dependent T cell synapses remains unknown. Here, we employ a supported-lipid bilayer system and TIRF microscopy to monitor the IL2R subunits and their spatiotemporal organization relative to T cell receptor (TCR) at the IS of CD8 ⁺ T cells. We show that TCR and IL2 signaling overlap in space and time and synergize when simultaneously triggered. Using Immuno-STATs, a class of immunotherapeutics in clinical testing that co-deliver IL2 and peptide major histocompatibility complex (pMHC), we demonstrate synergistic TCR and IL2R signaling that drives efficient expansion of antigen-specific CD8 ⁺ T cells. Together, these findings establish the IS as a platform for coordinated cytokine and antigen receptor signaling, providing a mechanistic framework for more selective antigen-specific immunotherapies.
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BibTeX
@article{capera2026spatiotemporal,
title = {{Spatiotemporal co-regulation of IL2 and TCR receptors reveals early antigen-driven synaptic synergy in human CD8+ T cells}},
author = {Jesusa Capera and María Navarro-Pérez and Ashwin K. Jainarayanan and Salvatore Valvo and Lina Chen and Panyu Fei and Sarah Flannery and Roman Fischer and Saso Cemerski and Simon Low and Steven N. Quayle and Raymond J. Moniz and Anish Suri and Michael L. Dustin},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-77110-1},
url = {https://www.nature.com/articles/s41467-026-77110-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Spatiotemporal co-regulation of IL2 and TCR receptors reveals early antigen-driven synaptic synergy in human CD8+ T cells
AU - Jesusa Capera
AU - María Navarro-Pérez
AU - Ashwin K. Jainarayanan
AU - Salvatore Valvo
AU - Lina Chen
AU - Panyu Fei
AU - Sarah Flannery
AU - Roman Fischer
AU - Saso Cemerski
AU - Simon Low
AU - Steven N. Quayle
AU - Raymond J. Moniz
AU - Anish Suri
AU - Michael L. Dustin
PY - 2026
DA - 2026/10/07
JO - Nature Communications
DO - 10.1038/s41467-026-77110-1
UR - https://www.nature.com/articles/s41467-026-77110-1
AB - Interleukin 2 (IL2) promotes T cell proliferation and differentiation, making it a central target in immunotherapies. Following antigen recognition, IL2 receptor (IL2R) signaling polarizes towards the immunological synapse (IS). However, how IL2 function is integrated during earlier antigen-dependent T cell synapses remains unknown. Here, we employ a supported-lipid bilayer system and TIRF microscopy to monitor the IL2R subunits and their spatiotemporal organization relative to T cell receptor (TCR) at the IS of CD8 ⁺ T cells. We show that TCR and IL2 signaling overlap in space and time and synergize when simultaneously triggered. Using Immuno-STATs, a class of immunotherapeutics in clinical testing that co-deliver IL2 and peptide major histocompatibility complex (pMHC), we demonstrate synergistic TCR and IL2R signaling that drives efficient expansion of antigen-specific CD8 ⁺ T cells. Together, these findings establish the IS as a platform for coordinated cytokine and antigen receptor signaling, providing a mechanistic framework for more selective antigen-specific immunotherapies.
SN - 2041-1723
ER -