Identification of the staphylococcal enterotoxin A superantigen binding site in the beta 1 domain of the human histocompatibility antigen HLA-DR.

The staphylococcal enterotoxin A (SEA) is a superantigen that must bind to class II molecules of the major histocompatibility complex to be recognized by T cells. In humans, most HLA-DR class II allelic and isotypic forms, such as DR1, bind SEA well. DRw53 is an exception, binding SEA very poorly. We have localized this difference to a single residue (amino acid 81) in the beta 1 domain. A highly conserved histidine at residue 81 allows SEA binding, but a tyrosine does not. Residue 81 is predicted to lie in an alpha-helix on the surface of the molecule, with its side chain pointing up out of the pocket associated with binding of conventional peptide antigens. This finding supports the hypothesis that superantigens and conventional antigens bind to different sites on the class II molecule.