T cell anergy prevents self-reactive T cells that escape elimination in the thymus from responding. T cell anergy is associated with decreased interleukin 2 (IL-2) production and decreased proliferation in response to antigen-specific stimulation. Hundt et al. show that although phosphorylation of the tyrosine kinase ZAP-70 is not impaired, phosphorylation of the ZAP-70 substrate, linker of activated T cells (LAT), is decreased. LAT serves as a scaffold recruiting various downstream effectors to the immunological synapse. Thus, lack of LAT phosphorylation prevents activation of phospholipase Cg1 (PLCg-1) and phosphatidylinositol 3-kinase (PI3K). There was no decrease in LAT abundance in the anergic cells, but LAT was selectively excluded from the immunological synapse because of reduced palmitoylation of LAT, which may explain the altered signaling properties in anergic T cells. — NG
Immunity 24, 513 (2006).