Cell-Cell Interactions are essential for multiple biological processes to run smoothly, including a variety of processes like embryonic development, immunity, and neuronal signaling. Cell-cell interaction dynamics can be monitored in vivo by using intravital microscopy, but this approach does not provide any information regarding the ligands and receptors involved or enable the isolation of interacting cells for downstream analysis. Now a complementary approach has come into the scene that uses bacterial sortase A-mediated cell labeling across synapses of immune cells to identify receptor-ligand interactions between cells in living mice. It works by generating a signal that can subsequently be detected ex vivo by flow cytometry. This approach for the labeling of ‘kiss-and-run’ interactions between immune cells is known as ‘Labelling Immune Partnerships by SorTagging Intercellular Contacts’ (LIPSTIC). Using LIPSTIC, scientists have shown that the interactions between dendritic cells and CD4+ T cells during T-cell priming in vivo occur in two distinct modalities. These two modalities are early, cognate stage, during which CD40–CD40L interactions occur specifically between T cells and antigen-loaded dendritic cells; and a later, non-cognate stage during which these interactions no longer require the prior engagement of T-cell receptor. Therefore, LIPSTIC enables the direct measurement of cell-cell interaction dynamics both in vitro and in vivo. Given the flexibility for use of this technique with different receptor-ligand pairs and a range of detectable labels, Scientists expect that this approach will be of use to any field of biology requiring quantification of intercellular communication.
