Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens

Similar to native peptide/MHC ligands, bacterial superantigens have been fo und to bind with low affinity to the T cell receptor (TOR). It has been hyp othesized that low ligand affinity is required to allow optimal TOR signali ng. To test this, we generated variants of Staphylococcus enterotoxin C3 (S EC3) with up to a 150-fold increase in TOR affinity. By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells. Thus, the potency of t he SEC3 variants correlated with enhanced binding without any optimum in th e binding range covered by native TCR ligands. Comparable studies using ant i-TCR antibodies of known affinity confirmed these observations. By compari ng the biological potency of the two sets of ligands, we found a significan t correlation between ligand affinity and ligand potency indicating that it is the density of receptor-ligand complexes in the T cell contact area tha t determines TCR signaling strength.