The Superantigen Streptococcal Pyrogenic Exotox in C ( SPE - C ) Exhibits a

Recombinant streptococcal pyrogenic exotoxin C (SPE-C) is a potent superantigen that stimulates VJ32-bearing human T cells, but is inactive in mice. SPE-C binds with high affinity to both human H L A D R and murine I-E molecules, but not to routine I-A molecules in a zincdependent fashion. Competition binding studies with other recombinant toxins revealed that SPE-C lacks the generic low affinity major histocompatibility complex (MHC) class II (x-chain binding site common to all other bacterial superantigens. Despite this, SPE-C cross-links M H C 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 M H C class II.