T-Cell Receptor Signaling to NF-κB

The activation of the nuclear factor kappa B (NF-κB) family of transcription factors is a key step in the adaptive immune response, in which lymphocytes respond to antigen by proliferating and generating multiple effector responses geared toward eradicating a pathogen. NF-κB activation is required for the proliferation, survival, and differentiation of lymphocytes, as well as the production of pro-inflammatory responses. NF-κB normally remains dormant in the cytosol, poised for activation. Multiple receptors can activate NF-κB, including antigen receptors on T and B cells. In the adaptive immune response, antigen receptor signaling leads to the activation of a signaling cascade that culminates in the activation of the IκB kinase (IKK) complex, which phosphorylates IκBs, marking them for destruction, allowing NF-κB to enter the nucleus and activate the transcription of genes involved in the immune response. This article provides an overview of the regulated signaling events in this pathway.