Pasqual, G. et al. Nature 553, 496–500 (2018).

Many immune processes depend on brief 'kiss-and-run' interactions between different cell types, but detecting the involvement of specific receptors and ligands has been a challenge. Pasqual et al. present LIPSTIC (labeling immune partnerships by SorTagging intercellular contacts), a method that detects receptor–ligand interactions between cells, even in living mice. The approach relies on the harnessing of bacterial sortase A, which is fused to a receptor (or ligand) of interest. A tag containing a 5-glycine N-terminal motif is fused to the complementary ligand (or receptor). Sortase A transfers a biotinylated or fluorescently labeled substrate peptide to this 5-glycine motif, thereby installing it on the ligand. Using this approach, the authors found that CD40–CD40L interactions between dendritic cells and CD4+ T cells occur at two different stages during T cell priming.