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

Streptococcal superantigen (SSA) is a 28,000 M-r toxin originally isolated from a pathogenic strain of Streptococcus pyogenes that has 60% sequence id entity with staphylococcal enterotoxin B (SEB). SSA and SEE, however, do no t compete for binding on the surfaces of cells expressing MHC class II mole cules, This behavior had been ascribed to SSA and SEE binding to distinct s ites on, or different subsets of, HLA-DR molecules. Here we demonstrate tha t SSA binds predominantly to HLA-DQ, rather than to HLA-DR molecules, and p resent the crystal structure of SSA at 1.85 Angstrom resolution. These data provide a structural basis for interpreting the interaction of SSA with HL A-DQ molecules as well as a foundation for understanding bacterial superant igen affinities for distinct MHC isotypes.