Immune cell interactions are a key component of immune surveillance and play a vital role in maintaining the body's defense against disease. Dendritic cells, rare yet potent antigen-presenting cells of the immune system, are central orchestrators of immune activation, bridging innate sensing and adaptive responses by priming and activating cytotoxic T cells. To precisely identify key immune cell subsets and enable modifications to enhance their immune response, new biotechnologies are needed to unravel the complexity of the tumor microenvironment.

GFP-based Touching Nexus (G-baToN) is a nanobody-directed fluorescent protein transfer based cell-cell interaction labeling technology that identifies interactions between cells. While G-baToN has been robustly tested in vitro with cell lines, it has yet to be integrated into primary mouse immune cells, which would enable a wider range for this technology to study immune cell interactions within disease models. To employ G-baToN in primary immune cells, transduction conditions were optimized specifically for mouse dendritic cells. Mouse CD8+ T cell transduction was additionally explored as a complementary system, given their functional coupling with dendritic cell early priming. This work provides a proof of concept for an in vivo mouse model of cell-cell interaction labeling between mouse dendritic cells and CD8+ T cells, establishing the foundation for dissecting the dendritic cell-driven immune response activation.