KINETIC DISCRIMINATION IN T-CELL ACTIVATION

We propose a quantitative model for T-cell activation in which the rat e of dissociation of ligand from T-cell receptors determines the agoni st and antagonist properties of the ligand. The ligands are molecular complexes between antigenic peptides and proteins of the major histoco mpatibility complex on the surfaces of antigen-presenting cells. Bindi ng of ligand to receptor triggers a series of biochemical reactions in the T cell. If the ligand dissociates after these reactions are compl ete, the T cell receives a positive activation signal. However, dissoc iation df ligand after completion of the first reaction but prior to g eneration of the final products results in partial T-cell activation, which acts to suppress a positive response. Such a negative signal is brought about by T-cell ligands containing the variants of antigenic p eptides referred to as T-cell receptor antagonists. Results of recent experiments with altered peptide ligands compare favorably with T-cell responses predicted by this model.