Cutting Edge: TCR Ligation Triggers Digital Activation of NF-κB

TCR-mediated activation of the transcription factor NFkB is required for T cell proliferation, survival, and effector differentiation. Although this pathway is the subject of intense study, it is not known whether TCR signaling to NF-kappa B is digital (switch-like) or analog in nature. Through analysis of the phosphorylation and degradation of I kappa B alpha and the nuclear translocation and phosphorylation of the NF-kappa B subunit RelA, we show that TCR-directed NF-kappa B activation is digital. Furthermore, digitization occurs well upstream of the I kappa B kinase complex, as protein kinase C theta translocation to the immunologic synapse and activation-associated aggregation of Bcl10 and Malt1 also demonstrate both digital behavior and high correlation with RelA nuclear translocation. Thus, similar to the TCR-to-MAPK signaling cascade, analog Ag inputs are converted to digital activation outputs to NF-kappa B at an early step downstream of TCR ligation. The Journal of Immunology, 2010, 185: 4520-4524.