The T lymphocyte response to pathogens is shaped by the T cell microenvironment and key environmental signals are provided by amino acids, glucose and oxygen. Environmental sensors in T cells include the nutrient-sensing serine/threonine kinases, adenosine monophosphate-activated protein kinase and mammalian target of rapamycin complex 1 and signaling pathways regulated by intracellular protein O-GlcNAcylation. Other environmental sensors are transcription factors such as c-myc and hypoxia-inducible factor-1 alpha.The present talk will explore the molecular basis for the impact of environmental signals on the differentiation of conventional T cell receptor αβ T cells and how the T cell response to immune stimuli can coordinate the T cell response to environmental cues.