Figure 1. Schematic of the T cell receptor proximal signaling molecules considered in the systems model.

We consider the TCR-chain containing three ITAMs, labelled as 3 (membrane-distal) to 1 (membrane-proximal). These ITAMs are sequentially phosphorylated by the tyrosine kinase Lck and dephosphorylated by the phosphatase CD45. The cytosolic kinase ZAP-70 contains tandem SH2 domains which are able to bind to doubly (fully) phosphorylated ITAMs with differential affinities, with the smallest affinity to 3 and largest affinity to 1. When bound to phosphorylated ITAMs, ZAP-70 is able to propagate signaling by phosphorylating downstream signaling molecules and adaptors.