The domain structure and functional relationships in the bacterial superantigen, SEB.
Staphylococcal enterotoxin B (SEB) has three essential biological properties that appear to be mediated by particular domains of the protein. As a superantigen, SEB triggers the T cell receptor (TcR) of a selected subset of T cells where the beta chain is encoded by particular V beta gene products. T cell triggering is generally dependent upon the ability of SEB to form a ternary complex with the TcR and MHC class II molecules and this interaction is relatively unrestricted by class II polymorphism. The third property of SEB is its potent toxicity; a few nanograms are sufficient to cause vomiting and violent diarrhoea in primates. In this study, we confirm the importance of the amino terminal domain of SEB for stimulation of human T cells. It is clear that the first 138 residues are the minimal mitogenic component of the toxin, and deletion of just seven more residues abrogates all activity. A mutant molecule with an internal deletion of these seven residues (SEB delta 131-138) was mitogenic suggesting that the region can confer stability to the rest of the protein, but does not include contact sites for either class II or the TcR. We further show that the disulphide loop is not essential for T cell recognition and that each of our mutants binds class II molecules with reduced affinity and is subtly variant in the pattern of TcR that it stimulates.
Hayball
J D
JD
Department of Immunology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
O'Hehir
R E
RE
Lamb
J R
JR
Lake
R A
RA
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D004768:Enterotoxins / Q000737:chemistry* / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D018089:Superantigens / Q000737:chemistry* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C031818:enterotoxin B, staphylococcal