Editors' ChoiceImmunology

Superantigens Activate an Alternative Pathway

Science's STKE  01 Aug 2006:
Vol. 2006, Issue 346, pp. tw254
DOI: 10.1126/stke.3462006tw254

Bacterial superantigens (SAg) bind T cell receptors (TCRs) to nonspecifically activate T cells, leading to a massive and potentially lethal immune response. In contrast to antigen-dependent TCR-mediated responses, bacterial SAg can activate T cells lacking Lck, a Src family tyrosine kinase; moreover, SAgs recognized in the context of major histocompatibility complex (MHC) class II molecules activate both CD4+ and CD8+ T cells. After confirming that neither CD4 nor Lck was required for SAg-dependent TCR-mediated interleukin-2 (IL-2) production, Bueno et al. showed that, in Lck-deficient T cells, antigen-presenting cells (APCs) pre-exposed to staphylococcus enterotoxin E (SEE-APCs) failed to elicit phosphorylation of such downstream effectors of antigen-dependent TCR signaling as ZAP-70, LAT, and phospholipase C-γ1 (PLC-γ1). A combination of pharmacological analysis, Western analysis, RNA interference, cell fractionation, and expression of a dominant-negative of the heterotrimeric guanine nucleotide-binding protein (GNBP) alpha subunit Gα11 indicated that, in Lck-deficient T cells, SEE-APCs activate Gα11, PLC-β, PKC (protein kinase C), the mitogen-activated protein kinases ERK1 and ERK2, and the transcription factors NFAT and NF-κB and also stimulate Ca2+ mobilization. Thus, the authors suggest that SAgs may signal through an alternative pathway initiated through their binding to both TCRs and a coreceptor coupled to Gα11.

C. Bueno, C. D. Lemke, G. Criado, M. L. Baroja, S. S. Ferguson, A. K. M. Nur-Ur Rahman, C. D. Tsoukas, J. K. McCormick, J. Madrenas, Bacterial superantigens bypass Lck-dependent T cell receptor signaling by activating a Gα11-dependent, PLC-β-mediated pathway. Immunity 25, 67-78 (2006). [PubMed]