Both high and low avidity antibodies to the T cell receptor can have agonist or antagonist activity

Anti-TCR antibodies can activate or block the activation of T cells. In the present experiments, we have shown that different monoclonal antibodies to the same TCR can have either agonist or antagonist activity, and we have examined the relationship between these functional effects and the avidity of the antibody for the TCR. We show here that it is not the avidity of an anti-TCR antibody that determines whether it acts as an agonist or an antagonist. Moreover, we show that monovalent Fab fragments of agonist antibodies produce detectable changes in T cell behavior. These data suggest that T cell activation may involve not just aggregation of the TCR but also some induced change in individual ligated receptors, and that agonists may produce this change while antagonists do not. We argue that similar effects may apply to peptide-MHC ligands as well.