Mammalian Target of Rapamycin Integrates Diverse Inputs To Guide the Outcome of Antigen Recognition in T Cells

T cells must integrate a diverse array of intrinsic and extrinsic signals upon Ag recognition. Although these signals have canonically been categorized into three distinct events-Signal 1 (TCR engagement), Signal 2 (costimulation or inhibition), and Signal 3 (cytokine exposure)-it is now appreciated that many other environmental cues also dictate the outcome of T cell activation. These include nutrient availability, the presence of growth factors and stress signals, as well as chemokine exposure. Although all of these distinct inputs initiate unique signaling cascades, they also modulate the activity of the evolutionarily conserved serine/threonine kinase mammalian target of rapamycin (mTOR). Indeed, mTOR serves to integrate these diverse environmental inputs, ultimately transmitting a signaling program that determines the fate of newly activated T cells. In this review, we highlight how diverse signals from the immune microenvironment can guide the outcome of TCR activation through the activation of the mTOR pathway. The Journal of Immunology, 2012, 188: 4721-4729.