There are several key differences between the nature of interactions of a T-cell receptor (TCR) with a conventional MHCpeptide complex and a bacterial superantigen (SAg). Apart from being powerful T-cell mitogens, these SAgs do not require antigen processing, they interact with the Vβ region of TCR and their binding sites lie outside the peptide-binding groove of the major histocompatibility complex (MHC) class II molecule (1-5). The plasticity of TCR binding to MHC-peptide complex has been appreciated only recently from crystal structures of TCR-MHC complex (6,7). However, the breadth of response to different MHCpeptide ligands is limited, whereas bacterial SAgs commonly interact with several Vβ elements. This results largely from the fact that much of the contact is with main-chain atoms instead of side-chain residues of TCR Vβ (5,8,9). Taking into account these differences and particularly the strength of the SAg effect on T-cell activation, it was reasonable to predict that bacterial SAgs would interact with higher affinity and that they would also show different binding kinetics.