Staphylococcal enterotoxin H displays unique MHC class II-binding properties.
Staphylococcal enterotoxin H (SEH) has been described as a superantigen by sequence homology with the SEA subfamily and briefly characterized for its in vivo activity. In this study, we demonstrate that SEH is a potent T cell mitogen and inducer of T cell cytotoxicity that possesses unique MHC class II-binding properties. The apparent affinity of SEH for MHC class II molecules is the highest affinity ever measured for a staphylococcal enterotoxin (Bmax1/2 approximately 0.5 nM for MHC class II expressed on Raji cells). An excess of SEA or SEAF47A, which has reduced binding to the MHC class II alpha-chain, is able to compete for binding of SEH to MHC class II, indicating an overlap in the binding sites at the MHC class II beta-chain. The binding of SEH to MHC class II is like SEA, SED, and SEE dependent on the presence of zinc ions. However, SEH, in contrast to SEA, binds to the alanine-substituted DR1 molecule, betaH81A, believed to have impaired zinc-bridging capacity. Furthermore, alanine substitution of residues D167, D203, and D208 in SEH decreases the affinity for MHC class II as well as its in vitro potency. Together, this indicates an MHC class II binding site on SEH with a different topology as compared with SEA. These unique binding properties will be beneficial for SEH to overcome MHC class II isotype variability and polymorphism as well as to allow an effective presentation on APCs also at low MHC class II surface expression.
Nilsson
H
H
Active Biotech Research AB, Department of Cell and Molecular Biology, Section for Tumor Immunology, Lund University, Sweden. helen.nilsson@activebiotech.com
Björk
P
P
Dohlsten
M
M
Antonsson
P
P
D000409:Alanine / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004768:Enterotoxins / Q000235:genetics / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding / Q000235:genetics; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000378:metabolism
D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; C402489:Staphylococcal enterotoxin H; D018089:Superantigens; D001224:Aspartic Acid; D015032:Zinc; D000409:Alanine