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SEC2-induced superantigen and antitumor activity is regulated through calcineurin

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Abstract

Once the TCR-SAg-MHC II ternary complex is established, it triggers a variety of intracellular signal transduction pathways, which provoke extreme responses in the immune system. However, the signaling events that involved in SAg-induced immune activation are not well understood. In this study, we demonstrated that the Ca2+/calcineurin (CaN)/nuclear factor of activated T cells (NFAT) signaling pathway was involved in SEC2-induced immune activation, and selective blockade of CaN by its inhibitor cyclosporine A (CsA) can completely inhibited the SEC2-induced T-cell stimulating potency. In addition, we selected an engineered SEC2 mutant named SAM-1 based on a series of biological activity tests, and our further studies on it not only confirmed that the CaN activity and gene transcription of its key substrates were proportional to the SEC2/SAM-1-induced T-cell stimulating potency, but also suggested that intensified Ca2+/CaN/NFAT signaling transduction induced by SAM-1 resulted in enhanced T-cell stimulating potency, production of cytokines and cytotoxicity, which finally elicit the improved antitumor activity of SAM-1 in vivo.

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Acknowledgments

This work was supported by grants from the National Science & Technology Major Specific Projects of China for “Significant Creation of New Drugs” (2012ZX09102301-013) and Science & Technology Projects of Shenyang China (F11-264-1-11, F12-152-9-00).

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The authors declare no financial or commercial conflict of interest.

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Authors and Affiliations

  1. Institute of Applied of Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis, P.O. Box 417, 110016, Shenyang, Liaoning, People’s Republic of China

    Yanli Liu, Mingkai Xu, Huiwen Zhang, Xu Li, Zhencheng Su & Chenggang Zhang

  2. University of Chinese Academy of Sciences, Beijing, People’s Republic of China

    Yanli Liu

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  1. Yanli Liu
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  2. Mingkai Xu
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  3. Huiwen Zhang
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  4. Xu Li
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Correspondence to Mingkai Xu.

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Liu, Y., Xu, M., Zhang, H. et al. SEC2-induced superantigen and antitumor activity is regulated through calcineurin. Appl Microbiol Biotechnol 97, 9695–9703 (2013). https://doi.org/10.1007/s00253-013-4764-6

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  • DOI: https://doi.org/10.1007/s00253-013-4764-6

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