Supplementary Figure 9: Schematic summary depicting the role of LAT residue 131 in controlling T cell signaling.
From: Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination
The top panel builds upon structural and biochemical analyses of ZAP-70 substrate recognition, which revealed that G131 in human LAT attenuates the rate of Y132 phosphorylation relative to that of other tyrosine phosphorylation events on LAT. The bottom panel depicts the implication for T cell ligand selectivity of the naturally slow Y132 phosphorylation found in mammalian T cells relative to more efficient Y132 phosphorylation in G131D/E mutant T cells and some fish T cells. The G131D mutation facilitates Y132 phosphorylation but also promotes self-reactivity. Mammals use G131 to attenuate Y132 phosphorylation for better ligand discrimination. Our results raise the possibility that some fish may utilize different LAT phosphorylation kinetics than most jawed vertebrates to alter the T cell activation threshold and achieve immune-fitness advantages in their environments for better T cell ligand discrimination.
