Putting the Pieces in Place

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Science  06 Feb 2009:
Vol. 323, Issue 5915, pp. 689
DOI: 10.1126/science.323.5915.689a

T cells require two signals, which are delivered via antigen-presenting cells, to be activated. The T cell receptor (TCR) engages major histocompatibility complexes that present peptides derived from pathogens, and the costimulatory receptor CD28 interacts with its ligand, B7. Engagement of CD28 is critical for T cells in distinguishing between foreign and self-antigens because antigen-presenting cells express high levels of B7 only during infection. Park et al. demonstrate that phosphoinositide-dependent kinase 1 (PDK1) integrates signals downstream of the TCR and CD28 to promote T cell activation through activation of the transcription factor NF-κB. PDK1-deficient T cells exhibited impaired TCR/CD28-induced activation and a selective impairment in NF-κB activation. In T cells, NF-κB is activated after the assembly of the CARMA1-Bcl10-MALT1 (CBM) complex that itself depends on protein kinase C-θ (PKC-θ). TCR signaling recruited PKC-θ to the immunological synapse, whereas CD28 signaling drove recruitment of PDK1 and its subsequent autophosphorylation. The phosphorylation of PDK1 facilitated its interaction with PKC-θ and CARMA1, resulting in their activation and the assembly of the CBM complex that leads to NF-κ B activation. — KM

Nat. Immunol. 10, 158 (2009).

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