Bacterial Superantigens Bypass Lck-Dependent T Cell Receptor Signaling by Activating a G[alpha]11-Dependent, PLC-[beta]-Mediated Pathway

• Published in: Immunity (Cambridge, Mass.) Mass.), 2006-07, Vol.25 (1), p.67
• Main Authors: Bueno, Clara, Lemke, Caitlin D, Criado, Gabriel, Baroja, Miren L, Ferguson, Stephen SG, Rahman, AKM Nur-Ur, Tsoukas, Constantine D, McCormick, John K, Madrenas, Joaquin
• Format: Article
• Language: English
• Subjects: Flow cytometry; Gene expression; Kinases; Lymphocytes; Medical research; Peptides; R&D; Research & development; T cell receptors; Transcription factors; Transplants & implants
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2006.04.012

The paradigm to explain antigen-dependent T cell receptor (TCR) signaling is based on the activation of the CD4 or CD8 coreceptor-associated kinase Lck. It is widely assumed that this paradigm is also applicable to signaling by bacterial superantigens. However, these bacterial toxins can activate human T cells lacking Lck, suggesting the existence of an additional pathway of TCR signaling. Here we showed that this alternative pathway operates in the absence of Lck-dependent tyrosine-phosphorylation events and was initiated by the TCR-dependent activation of raft-enriched heterotrimeric Gα11 proteins. This event, in turn, activated a phospholipase C-β and protein kinase C-mediated cascade that turned on the mitogen-activated protein kinases ERK-1 and ERK-2, triggered Ca2+influx, and translocated the transcription factors NF-AT and NF-κB to the nucleus, ultimately inducing the production of interleukin-2 in Lck-deficient T cells. The triggering of this alternative pathway by superantigens suggests that these toxins use a G protein-coupled receptor as a coreceptor on T cells.