B and T cells recognize the antigen thanks to their specific receptor and form a special signaling platform (the immune synapse) when in contact with a so called “antigen presenting cell”. After synapse formation, the lymphocyte accumulates the antigen at the center of the contact and reorganizes its organelles to polarize, ultimately enabling to perform its immune function (antigen extraction and processing for B cell, killing for cytotoxic T cells, activation for CD4 T cells). Understanding what controls the dynamics of immune synapse formation, the polarization of the cell and the response of the immuen cells is therefore a crucial step in improving or modulate antibody production (B cells), T cell activation (CD4 T cells) and target killing (cytotoxic T cells and CAR-T).
To study what happen to the B or T cell when it interacts with the antigen presneting cells we introduce a pairing cell microfluidic chip that allows multiple simultaneous observations of synapse formation. To modulate the different physico-chemical properties of the presenting cell, we develop and characterize a new material, the lipid droplet, whose features (size, surface tension, fluidity, ligand concentration) can be easily controlled and that can be used as force sensor. By presenting the antigen on functionalised oil droplets and trapping doublets (droplets – B cell) in microfluidic traps we could follow multiple polarization events and investigate the polarization kinetics (what comes first?) and the interplay between actin and microtubules networks (what controls what?) in the formation of a functional synapse. Using quantitative live imaging, we can characterize the movement of most major actors upon antigen recognition from the first contact, and the impact of drugs targeting the cytoskeleton on their polarization dynamics. We will apply this new set of experimental and analytical tools to investigate the polarization and signaling dynamics of differnet cells. This can also open up perspective in understanding the fundamental processes used by cells in recent cancer immunotherapies.