2xn9 Citations

The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation.


Superantigens (SAgs) are bacterial toxins that interact with immunoreceptors, T cell receptor (TCR) and major histocompatibility complex (MHC) class II, conventionally through the variable β-domain of TCR (TCRVβ). They induce a massive release of cytokines, which can lead to diseases such as food poisoning and toxic shock syndrome. In this study, we report the X-ray structure of the ternary complex between staphylococcal enterotoxin H (SEH) and its human receptors, MHC class II and TCR. The structure demonstrates that SEH predominantly interacts with the variable α-domain of TCR (TCRVα), which is supported by nuclear magnetic resonance (NMR) analyses. Furthermore, there is no contact between MHC and TCR upon complex formation. Structural analyses suggest that the major contact points to TCRVα are conserved among other bacterial SAgs. Consequently, a new dimension of SAg biology emerges, suggesting that in addition to the conventional interactions with the TCRVβ domain, SAgs can also activate T cells through the TCRVα domain.

Reviews citing this publication (3)

  1. Soluble T cell receptor Vβ domains engineered for high-affinity binding to staphylococcal or streptococcal superantigens. Sharma P, Wang N, Kranz DM. Toxins (Basel) 6 556-574 (2014)
  2. T cells and their eons-old obsession with MHC. Yin L, Scott-Browne J, Kappler JW, Gapin L, Marrack P. Immunol. Rev. 250 49-60 (2012)
  3. Gram-positive bacterial superantigen outside-in signaling causes toxic shock syndrome. Brosnahan AJ, Schlievert PM. FEBS J. 278 4649-4667 (2011)

Articles citing this publication (10)

  1. A comprehensive mathematical model for three-body binding equilibria. Douglass EF, Miller CJ, Sparer G, Shapiro H, Spiegel DA. J. Am. Chem. Soc. 135 6092-6099 (2013)
  2. Compound heterozygosity of HLA-DRB3*01:01 and HLA-DRB4*01:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia. Loewenthal R, Rosenberg N, Kalt R, Dardik R, Landau M, Yahalom V, Avishai O, Frenkel O, Gazit E, Steinberg DM, Lipitz S, Salomon O. Transfusion 53 344-352 (2013)
  3. Clarifying the mechanism of superantigen toxicity. Fraser JD. PLoS Biol. 9 e1001145 (2011)
  4. Structure of Staphylococcal Enterotoxin E in Complex with TCR Defines the Role of TCR Loop Positioning in Superantigen Recognition. Rödström KE, Regenthal P, Lindkvist-Petersson K. PLoS ONE 10 e0131988 (2015)
  5. The tumor targeted superantigen ABR-217620 selectively engages TRBV7-9 and exploits TCR-pMHC affinity mimicry in mediating T cell cytotoxicity. Hedlund G, Eriksson H, Sundstedt A, Forsberg G, Jakobsen BK, Pumphrey N, Rödström K, Lindkvist-Petersson K, Björk P. PLoS ONE 8 e79082 (2013)
  6. Inhibition of emetic and superantigenic activities of staphylococcal enterotoxin A by synthetic peptides. Maina EK, Hu DL, Asano K, Nakane A. Peptides 38 1-7 (2012)
  7. Uptake and intracellular trafficking of superantigens in dendritic cells. Ganem MB, De Marzi MC, Fernández-Lynch MJ, Jancic C, Vermeulen M, Geffner J, Mariuzza RA, Fernández MM, Malchiodi EL. PLoS ONE 8 e66244 (2013)
  8. Pfit is a structurally novel Crohn's disease-associated superantigen. Liu L, Chen H, Brecher MB, Li Z, Wei B, Nandi B, Zhang J, Ling H, Winslow G, Braun J, Li H. PLoS Pathog. 9 e1003837 (2013)
  9. The construction of a bifunctional fusion protein consisting of SEC2 and EGFP. Liu Y, Xu M, Li X, Sun J, Zhang C, Zhang H. Biotechnol. Appl. Biochem. 61 565-571 (2014)
  10. Two common structural motifs for TCR recognition by staphylococcal enterotoxins. Rödström KE, Regenthal P, Bahl C, Ford A, Baker D, Lindkvist-Petersson K. Sci Rep 6 25796 (2016)