Characterization of the Complexity of Signaling Complexes in Human T Cells

Characterization of the Complexity of Signaling Complexes in Human T Cells

The activation of the T cells via the T cell antigen receptor (TCR) is required for the adaptive immune response to infection and the pathogenesis of numerous human diseases. The stimulation of the TCR induces the formation of intracellular signaling complexes that are needed for the activation of downstream functions. One protein critical for the nucleation of TCR-induced signaling complexes is the adaptor protein LAT. Upon TCR stimulation, LAT is phosphorylated on several conserved tyrosines, which then serve as binding sites for signaling proteins. The interaction of LAT with these proteins induces the formation of large mega-dalton-sized complexes. I will discuss our biophysical and biochemical studies of the formation and function of LAT-mediated complexes. These studies have highlighted the complex mechanism that controls the nucleation of signaling complexes in human T cells.