The palmitoylation switch in activated T cells. Reversible palmitoylation acts as a signal for the membrane anchoring and partitioning of approximately 250 proteins in T cells. It is catalyzed by the action of palmitoyl transferases (PAT’s) of the DHHC zinc finger family of proteins. A subset of proteins such as VAMP7 or the PAT’s themselves are found to be specifically palmitoylated upon T cell receptor activation. We will to use clickable palmitate variants and caged bromo-palmitate to acutely manipulate the palmitoylation switch in T cells after receptor engagement. Lipidomic and proteomic analysis will provide insights into the microenvironment of these acylated proteins and the role of de novo palmitoylation for T cell function will be probed at the cellular level and in a mouse model of anergy.