sketch of four phases in T cell signaling for four different types of activation. Each phase was delineated as a time window in our computer simulation [4]. For small numbers of ligands, kinetic proofreading and nonlinear delays in MAPK activation are sufficient to create an all-or-none discrimination between strong (row 1 – phase IV) and weak ligands (row 2 – phase IV). For large numbers of ligands, negative feedback through SHP-1 activation (Phase III) gets activated: for weak ligands, this feedback abrogates the signaling response (row 4 – phase IV) while for strong ligands, this feedback is insufficient to block all signaling, allowing the activation of MAPK cascade (row 3 – phase III), subsequent protection from pSHP-1 and signal maintenance (row 3 – phase IV).