Abstract

We are interested in the receptor-mediated signals that regulate the activation and function of T-cells. The antigen-receptor complex (TCR) activates T-cells via the activation of src kinases and ZAP -70 leading to the phosphorylation of the adaptor protein linker for the activation of T-cells (LAT). Despite its importance, it has been unclear whether LAT is solely coupled to the TCR , or whether it can undergo changes in composition in the regulation of T-cell function.

I will present data showing that co-receptors can alter the composition of the LAT signalosome by displacing associated GADs-SLP-76 complexes. These observations show for the first time that co-receptors can intersect directly with TCR signaling by altering the composition of the LAT signalosome in T-cells.

In the second part of my talk, I will discuss recent work showing that the adaptors can directly bind and modulate the nuclear pore complex (NPC) in T-cells for the transport of transcription factors such as NFAT , needed for the production of pro-inflammatory cytokines.