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.
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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.
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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
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DOI: https://doi.org/10.1038/5809
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