Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function

The role of CD26 in human T cell biology is puzzling. Despite being extensively characterized, it has been called ‘a moonlighting protein’ since it has multifunctional effects, but a definitive native ligand has not been identified. We summarize the current knowledge on the molecular mechanisms of CD26-mediated T cell costimulation and immune regulation. Work identifying a ligand for CD26 and elucidating the proximal signaling events associated with CD26-mediated T cell costimulation is also described. Finally, we discuss the involvement of CD26 in various pathophysiologic states as well as its suitability as a potential therapeutic target in selected immune diseases.