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Infection and Immunity, February 2001, p. 875-884, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.875-884.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Inhibition of Bacterial Superantigens by Peptides and Antibodies

Kumar Visvanathan,1 Alain Charles,1 Jason Bannan,2 Pavel Pugach,1 Khosrow Kashfi,1,3 and John B. Zabriskie1,*

Laboratory of Clinical Microbiology and Immunology, Rockefeller University, New York, New York 100211; Bacteriology Section American Type Culture Collection. Manassas, Virginia 201102; and Department of Physiology and Pharmacology, City University of New York Medical School, New York, New York 100313

Received 9 August 2000/Returned for modification 28 September 2000/Accepted 1 November 2000

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.

* Corresponding author. Mailing address: Laboratory of Clinical Microbiology and Immunology, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8155. Fax: (212) 327-7579. E-mail: zabrisk{at}rockvax.rockefeller.edu.

Infection and Immunity, February 2001, p. 875-884, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.875-884.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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