Distinct NF-kB activation pathways engaged by T-cell receptor and co-receptor CD28 on T-cells

The transcription factor nuclear factor-kB (NF-kB) is critical for the induction of inflammatory responses in T-cells, survival and differentiation.  Antigen receptor (TCR) and co-receptor CD28 are the central regulators of NF-kB activation in T-cells. Progress in understanding NF-kB activation in T-cells has occurred over the years with the identification of individual adapters such as ADAP and GRB-2 and enzymes such as PKC-θ that regulate NF-kB.  However, little is known whether the engagement of distinct modules by the TCR and CD28 account for the cooperative effects of the two receptors in activating NF-kB.  In this review, we discuss recent advances in our understanding of NF-kB regulation by TCR and CD28.