Project 1 | Dynamic videonanoscopy of the interactions between T cells and thymic epithelial cells
Collaboration with Magali Irla, Ciml
Medullary thymic epithelial cells (mTEC) control the development of immunocompetent T cells. Reciprocally, developing T cells control mTEC differentiation. The receptor RANK expressed by mTEC and its ligand RANKL provided by T cells play a key role in this thymic crosstalk by promoting the proliferation and differentiation of mTEC capable of sustaining the generation of a self-tolerant T-cell repertoire. Considering the importance of the RANK signaling axis in the thymic crosstalk, we will characterize at the single molecule level the dynamics of RANK and RANKL molecules at the immune synapse. We developed fluorescence videonanoscopy, which allows detecting single molecule motion with nanometer accuracy. The analysis of molecular trajectories will allow identifying interaction events at T cell/mTEC contacts. Ultra-resolved measurements will document the stabilization of contacts during this complex cellular interplay, which is fundamental for T-cell development and selection.
Immune synapse interactions studied by single molecule measures
The goal is to document the dynamics of RANK/RANKL interactions at the molecular scale at the immune synapse between murine or human thymic epithelial cell lines and primary T cells (isolated from mice or patients). The dynamics of this receptor/ligand pair will be analyzed at single molecule level by videonanoscopy. We will analyze the impact of blocking RANK signaling on RANK/RANKL molecular dynamics at the immune synapse.
Single molecule tracking of ligands and receptors by MTT2col