Inhibition of bacterial superantigens by peptides and antibodies.
The pyrogenic exotoxins of group A streptococci and staphylococcal enterotoxins are a family of structurally related superantigens with similar biological activity. Two distinct areas have been identified which have a highly conserved amino acid homology in all of the toxin families. A number of peptides were constructed from these regions, some of which were concatenated and polymerized to enhance their immunogenicity in animals. Antibodies prepared against these polymerized peptides were used to serologically identify the majority of the superantigen toxins, block the biological activities of the superantigens, and protect an experimental animal model against shock. In addition certain peptides were able per se to block up to 90% of the proliferative responses induced by the toxins. The peptide also proved protective in a septic shock model in mice. Binding experiments indicate that the peptide binds tightly to the major histocompatibility complex class II molecule, thus preventing binding and hence activation of the superantigen. The selective and rapid binding of the peptide to the major histocompatibility complex class II molecule may lead to a novel therapeutic modality in treatment of superantigen-mediated diseases.
Visvanathan
K
K
Laboratory of Clinical Microbiology and Immunology, Rockefeller University, New York, New York 10021, USA.
Charles
A
A
Bannan
J
J
Pugach
P
P
Kashfi
K
K
Zabriskie
J B
JB
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D015153:Blotting, Western; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D012772:Shock, Septic / Q000209:etiology / Q000517:prevention & control; D013210:Staphylococcus / Q000276:immunology*; D013291:Streptococcus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*
D000906:Antibodies; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D018089:Superantigens