Journal of Experimental Medicine, Vol 175, 387-396, Copyright © 1992 by Rockefeller University Press

ARTICLES

Mutations defining functional regions of the superantigen staphylococcal enterotoxin B

JW Kappler, A Herman, J Clements and P Marrack
Howard Hughes Medical Institute, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80207.

Staphylococcal enterotoxin B (SEB) is both a superantigen and toxin. As a superantigen, SEB can bind to major histocompatibility complex (MHC) class II molecules to form a ligand for alpha/beta T cell receptors bearing particular V beta elements. As a toxin, SEB causes rapid weight loss in mice sometimes leading to death. We show here that both of these functions map to the NH2-terminal portion of the toxin. Three regions were identified: one important in MHC class II binding, one in T cell recognition, and one in both functions. These results support the conclusion that the toxicity of SEB is related to massive T cell stimulation and release of cytokine mediators and show that the residues interacting with MHC and the T cell receptor are intertwined.
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