By Esther Landhuis
The mammalian immune system is a sprawling network of cells, each with unique properties and functions. As discussed in my latest Technology Feature, immunologists have developed a range of technologies to characterize those populations, from mass cytometry to single-cell DNA sequencing.
But the immune system is, in fact, a system, and its members don’t act alone. Immune activity depends upon cell-to-cell interaction, as when a dendritic cell cozies up to a T cell and activates it, or when a T cell run-in prompts a B cell to make antibodies. “When those cells meet physically, that’s when you start an immune response,” explains Gabriel Victora, an immunologist at Rockefeller University in New York.
Victora and coworkers came up with a clever way to track these sorts of kiss-and-run incidents using a method they’ve aptly named LIPSTIC (Labelling Immune Partnerships by SorTagging Intercellular Contacts). The system is designed such that an interaction between protein receptors on two cells — from a dish or a mouse — triggers an enzymatic reaction that tags one of the cells with a tell-tale reporter molecule. That tag – a five amino-acid peptide capped with biotin – is like lipstick on a paramour’s collar, Victora says: “You know there has been an interaction if you put ‘lipstick’ on one cell and it shows up on the other.”
In a study published in January in Nature, the Rockefeller team used the LIPSTIC approach to study interactions between dendritic cells and CD4+ helper-T cells in transgenic mice – interactions that are critical for jumpstarting CD8+ killer-T cells in response to immunization. “Within one lymph node we could detect the dozen or so dendritic cells that were starting an immune response,” Victora says.
Immunologist Scott Mueller of the University of Melbourne in Australia is also using LIPSTIC mice to determine how dendritic cells signal to CD4+ T cells – but his group is examining immune responses to viral infection. By visualising these cellular interactions in real-time with intravital microscopy, “we hope LIPSTIC will help us identify the types of interactions between cells that we cannot ‘see’ by other methods,” Mueller says.
At this point LIPSTIC mice are set up to analyze cell-cell interactions mediated by the pairing of CD40 and CD40L surface proteins, which are found on antigen-presenting cells and activated T cells, respectively. Victora’s group plans to create additional LIPSTIC strains to analyze other receptor-ligand pairs of interest to immunologists. So far they have distributed the CD40-CD40L mice or reagents to about a dozen labs.
Esther Landhuis is a freelance science journalist in the San Francisco Bay area.