Cutting edge: Trimolecular interaction of TCR with MHC class II and bacterial superantigen shows a similar affinity to MHC : peptide ligands

Bacterial superantigens such as Staphylococcus aureus enterotoxin A (SEA) a re very potent stimulators of T cells. They bind to the V beta region of th e TCR and to MRC class II, stimulating T cells at nanomolar concentrations. Using surface plasmon resonance measurements, we find that binding between the individual components of the complex (TCR-class II, TCR-SEA, SEA-class II) is very weak, but that the stability of the trimolecular complex is co nsiderably enhanced, reaching an affinity similar to that found for TCR int eractions with MHC:peptide ligand. Thus, the potency of SEA in stimulation of T cells is not due to particularly strong affinities between the protein s, but to a cooperative effect of interactions in the TCR-SEA-MHC class II trimolecular complex that brings the kinetics into a similar range to bindi ng of conventional Ags. This range may be the optimum for T cell activation .