Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 1 August 2006
Vol. 2006, Issue 346, p. tw254
[DOI: 10.1126/stke.3462006tw254]

EDITORS' CHOICE

IMMUNOLOGY Superantigens Activate an Alternative Pathway

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-{gamma}1 (PLC-{gamma}1). 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-{kappa}B 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]

Citation: Superantigens Activate an Alternative Pathway. Sci. STKE 2006, tw254 (2006).



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882