Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Structural basis for HLA–DQ binding by the streptococcal superantigen SSA

Nature Structural Biology volume 6, pages 123–129 (1999)Cite this article

Abstract

Streptococcal superantigen (SSA) is a 28,000 Mr toxin originally isolated from a pathogenic strain of Streptococcus pyogenes that has 60% sequence identity with staphylococcal enterotoxin B (SEB). SSA and SEB, however, do not compete for binding on the surfaces of cells expressing MHC class II molecules. This behavior had been ascribed to SSA and SEB binding to distinct sites on, or different subsets of, HLA–DR molecules. Here we demonstrate that SSA binds predominantly to HLA–DQ, rather than to HLA–DR molecules, and present the crystal structure of SSA at 1.85 Å resolution. These data provide a structural basis for interpreting the interaction of SSA with HLA–DQ molecules as well as a foundation for understanding bacterial superantigen affinities for distinct MHC isotypes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: SSA and SEB binding to MHC class II–expressing cell lines.
Figure 2: Crystallographic analysis of the refined SSA structure.
Figure 3: Structural comparisons of the MHC class II binding motifs in SEB and SSA.
Figure 4: SSA residues responsible for HLA–DQ affinity and specificity.

Similar content being viewed by others

References

  1. Scherer, M.T. et al. Ann. Rev. Cell Biol. 9, 101–128 (1993).

    Article  CAS  Google Scholar 

  2. Kotzin, B.L., Leung, D.Y., Kappler, J. & Marrack, P. Adv. Immunol. 54, 99–165 (1993).

    Article  CAS  Google Scholar 

  3. Conrad, B. et al. Cell 90, 303–313 (1997).

    Article  CAS  Google Scholar 

  4. Renno, T. & Acha–Orbea, H. Immunol. Rev. 154, 175–191 (1996).

    Article  CAS  Google Scholar 

  5. Jardetzky, T.S. et al. Nature 368, 711–718 (1994).

    Article  CAS  Google Scholar 

  6. Kim, J., Urban, R.G., Strominger, J.L. & Wiley, D.C. Science 266, 1870–1874 (1994).

    Article  CAS  Google Scholar 

  7. Kozono, H., Parker, D., White, J., Marrack, P. & Kappler, J. Immunity 3, 187–196 (1995).

    Article  CAS  Google Scholar 

  8. Thibodeau, J. et al. Science 266, 1874–1878 (1994).

    Article  CAS  Google Scholar 

  9. Lavoie, P.M. et al. Proc. Natl. Acad. Sci. USA 94, 6892–6897 (1997).

    Article  CAS  Google Scholar 

  10. Stevens, K.R., Van, M., Lamphear, J.G. &nd Rich, R.R. J. Immunol. 157, 4970–4978 (1996).

    CAS  PubMed  Google Scholar 

  11. Toyosaki, T. et al. Eur. J. Immunol. 26, 2693–2701 (1996).

    Article  CAS  Google Scholar 

  12. Norrby–Teglund, A. et al. Infect. Immun. 62, 5227–5233 (1994).

    PubMed  PubMed Central  Google Scholar 

  13. Esaki, Y. et al. Infect. Immun. 62, 1228–1235 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Busch, R., Cloutier, I., Sékaly, R.–P. & Hämmerling, G.J. EMBO J. 15, 418–428 (1996).

    Article  CAS  Google Scholar 

  15. Mollick, J.A. et al. J. Clin. Invest. 92, 710–719 (1993).

    Article  CAS  Google Scholar 

  16. Deringer, J.R., Ely, R.J., Stauffacher, C.V. & Bohach, G.A. Mol. Microbiol. 22, 523–534 (1996).

    Article  CAS  Google Scholar 

  17. Abrahmsén, L. et al. EMBO J. 14, 2978–2986 (1995).

    Article  Google Scholar 

  18. Hudson, K.R. et al. J. Exp. Med. 182, 711–720 (1995).

    Article  CAS  Google Scholar 

  19. Clackson, T. & Wells, J.A. Science 267, 383–386 (1995).

    Article  CAS  Google Scholar 

  20. Fremont, D.H. et al. Immunity 8, 305–317 (1998).

    Article  CAS  Google Scholar 

  21. Scott, C.A., Peterson, P.A., Teyton, L. & Wilson, I.A. Immunity 8, 319–329 (1998).

    Article  CAS  Google Scholar 

  22. Kabsch, W. J. Appl. Crystallogr. 21, 916 (1988).

    Article  CAS  Google Scholar 

  23. Otwinowski, Z. Data collection and processing (Warrington, UK; 1993).

    Google Scholar 

  24. Navaza, J. Acta Crystallogr. A50, 157–163 (1994).

    Article  CAS  Google Scholar 

  25. Collaborative Computational Project No. 4. Acta Crystallogr. D50, 760–763 (1994).

  26. Read, R.J. Acta Crystallogr. A42, 140–149 (1986).

    Article  CAS  Google Scholar 

  27. Brünger, A.T. XPLOR, V3.1 (Yale University Press, New Haven, Connecticut; 1992).

    Google Scholar 

  28. Jones, T.A., Zou, J.Y., Cowan, S.W. & Kjeldgaard, M. Acta Crystallogr. A 47, 110–119 (1991).

    Article  Google Scholar 

  29. Evans, S.V. J. Mol. Graphics 11, 131–138 (1993).

    Article  Google Scholar 

  30. Kraulis, P.J. J. Appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  31. Nicholls, A., Sharp, K. and Honig, B. Proteins 11, 281ff (1991).

    Article  Google Scholar 

Download references

Acknowledgements

We thank K.R. Stevens and R. Rich for the kind contribution of the SSA–expressing E. coli strain, L. Gu for the L243 antibody, D. Wiley for the CHAMP antibody, L. Bermann for assistance at the BNL–NSLS X–25A beamline, as well as P. Lavoie and R–P. Sékaly for provision of cell lines and for hosting E.S. in the Sékaly laboratory (Montreal, Quebec, Canada) in order to learn the experimental techniques of the cell binding assay. We also thank S. Garman and P. Lavoie for careful reading of, and editorial comments on, the manuscript. E.S. is supported by a grant from the NIH. This work has been funded by a grant from the NIH and an award from the Human Frontier Science Program.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanstown, 60208, Illinois, USA

    Eric Sundberg & Theodore S. Jardetzky

Authors
  1. Eric Sundberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Theodore S. Jardetzky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Theodore S. Jardetzky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sundberg, E., Jardetzky, T. Structural basis for HLA–DQ binding by the streptococcal superantigen SSA. Nat Struct Mol Biol 6, 123–129 (1999). https://doi.org/10.1038/5809

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/5809

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing