Molecular Interactions During T Cell Activation

The interests of my lab are centered on the basis of T cell activation through the T cell receptor during thymocyte development and the immune response. A major aspect of our current work is real-time imaging of molecular interactions during T cell activation, using fluorescent chimeras between cell surface or intracellular proteins and variants of the green fluorescent protein. Live cell deconvolution microscopy allows visualization of movements of these proteins into the immunological synapse during T cell activation, and, using fluorescence resonance energy transfer (FRET) between the fluorescent proteins, we can watch interactions between the proteins. During T cell activation, the T cell receptor must distinguish the few antigenic ligands from a vastly greater number of very similar, but non-stimulatory endogenous ligands. We have found that these non-stimulatory ligands in fact aid in the recognition of the antigenic ligand, and we are now seeking to understand the molecular basis of this phenomenon, as this is critical to understanding the basis of T cell activation. We recently discovered a new T cell specific protein that is necessary for T cell receptor-mediated signal transduction. The thymic positive selection process is defective in the absence of this gene, but the signaling pathway involved seems to be novel. Identifying how this molecule works is a new focus of the lab and is using a wide range of immunological, molecular genetic, biochemical and imaging tools.