STAPHYLOCOCCAL ENTEROTOXIN-A AND ENTEROTOXIN-B SHARE A COMMON STRUCTURAL MOTIF FOR BINDING CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES

A comparative site-directed mutagenesis study of staphylococcal entero toxins A and B was undertaken to identify key amino-acid residues whic h govern interactions with major histocompatibility class II molecules . This involved generating a three-dimensional homology model for ente rotoxin A in complex with the HLA-DR1 molecule, based on the reported X-ray crystal structures of enterotoxin B, both free and bound to HLA- DR1. A binding motif previously described for enterotoxin B was found to be conserved in enterotoxin A. An examination of the experimental d ata with the homology model clarifies how T-cell responses to enteroto xin A, and most bacterial superantigens, are likely to be mediated by variations of a structurally conserved HLA-DR alpha binding motif.