J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/08/375/09 $2.00
Volume 186, Number 3, August 4, 1997 375-383

The Superantigen Streptococcal Pyrogenic Exotoxin C (SPE-C) Exhibits a Novel Mode of Action

By Pei-Lin Li, Rodger E. Tiedemann, S. Louise Moffat, and John D. Fraser

From the Department of Molecular Medicine, University of Auckland, 92019 Auckland, New Zealand

Recombinant streptococcal pyrogenic exotoxin C (SPE-C) is a potent superantigen that stimulates V2-bearing human T cells, but is inactive in mice. SPE-C binds with high affinity to both human HLA-DR and murine I-E molecules, but not to murine I-A molecules in a zinc-dependent fashion. Competition binding studies with other recombinant toxins revealed that SPE-C lacks the generic low affinity major histocompatibility complex (MHC) class II -chain binding site common to all other bacterial superantigens. Despite this, SPE-C cross-links MHC class II to induce homotypic aggregation of class II-bearing B cells. Nondenaturing sodium dodecyl sulfate electrophoresis and size exclusion chromatography revealed that both wild-type and recombinant SPE-C exist in a stable dimer at neutral or alkaline pH. These data support a recent crystal structure of SPE-C and reveal yet another mechanism by which bacterial superantigens ligate and cross-link MHC class II.

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