THE SUPERANTIGEN STREPTOCOCCAL PYROGENIC EXOTOXIN-C (SPE-C) EXHIBITS A NOVEL MODE OF ACTION

Recombinant streptococcal pyrogenic exotoxin C (SPE-C) is a potent sup erantigen that stimulates V beta 2-bearing human T cells, but is inact ive in mice. SPE-C binds with high affinity to both human HLA-DR and m urine I-E molecules, but not to murine I-A molecules in a zinc-depende nt fashion. Competition binding studies with other recombinant toxins revealed that SPE-C lacks the generic low affinity major histocompatib ility complex (MHC) class II or-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. Nondenat uring sodium dodecyl sulfate electrophoresis and size exclusion chroma tography revealed that both wild-type and recombinant SPE-C exist in a stable dimer at neutral or alkaline pH. These data support a recent c rystal structure of SPE-C and reveal yet another mechanism by which ba cterial superantigens ligate and cross-link MHC class II.