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The Journal of Immunology, 1999, 162: 4550-4559.
Copyright © 1999 by The American Association of Immunologists

Unique Superantigen Activity of Staphylococcal Exfoliative Toxins1

Steven R. Monday*, Gregory M. Vath{ddagger}, Witold A. Ferens*, Claudia Deobald*, James V. Rago{dagger}, Pamala J. Gahr{dagger}, Dileep D. Monie{dagger}, John J. Iandolo§, Stephen K. Chapes, William C. Davis||, Douglas H. Ohlendorf{ddagger}, Patrick M. Schlievert{dagger} and Gregory A. Bohach2,*

* Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, ID 83844; Departments of {dagger} Microbiology and {ddagger} Biochemistry, University of Minnesota Medical School, Minneapolis, MN 55455; § Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190; Division of Biology, Kansas State University, Manhattan, KS 66506; and || Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164

Certain strains of Staphylococcus aureus express one or both of two related, but immunologically distinct, exfoliative toxins (ETA and ETB). These toxins induce the symptoms associated with staphylococcal scalded skin syndrome. Both ETs have been shown to stimulate T cell proliferation. Recently, it was reported that ETA is a superantigen that stimulates T cells bearing human Vß2 or several murine Vßs. However, other investigators have proposed that the superantigenicity reported for ETA resulted from contaminants in commercial preparations. This present study addresses those conflicting reports by assessing the biological and immunologic activities of highly purified rETs. ETA and ETB required APCs to induce selective polyclonal expansion of several human Vßs (huVßs), although, neither toxin expanded huVß2. ETB induced expansion of murine T cells bearing Vßs 7 and 8, those that have the highest homology to the huVßs expanded by ETA and ETB. Although flow cytometry of ETB-stimulated T cells matched PCR results, stimulation by ETA reduced percentages of T cells positive for several huVßs that had been shown to have increased levels of mRNA transcripts. ETA and ETB induced contrasting reactions in vivo. In rabbits, ETB was moderately pyrogenic and enhanced susceptibility to lethal shock, while ETA lacked both activities. Predictions based on comparisons with other superantigens suggest molecular regions potentially involved in receptor binding in the ETA crystal structure and a modeled ETB three-dimensional structure. These results show that ETs are superantigens with unique properties that could account for the discrepancies reported.




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