Canonical and non-canonical Notch signaling in CD4⁺ T cells

For T cells to become fully activated, they must integrate a myriad of signals, both extrinsic and intrinsic. External stimuli accrued through various cell surface receptors are transduced and amplified through a coordinated circuitry of signaling cascades that ultimately result in the transcription of new genes. Along the way, extracellular and intracellular signaling components function to impart a fully activated state. Evidence is accumulating to show that the Notch family of cell surface receptors, long known to function as transcriptional regulators through their interactions with the canonical nuclear binding protein CSL/RBP-J, may also be playing an as-yet-unappreciated role in T cell activation by virtue of its signaling via non-canonical as well as nonnuclear mechanisms. In this review we will discuss these and other better-known means by which Notch signaling influences T cell responses.