T cell-specific activation requires ligation of TCRs with peptide-MHC complexes on the APC. On the basis of simple chemical and statistical laws, we have constructed a mathematical model to describe this trimolecular interaction between effector and target cells, and we demonstrate its predictive value in the case of in vitro peptide Ag titration. Moreover, this model can generate mechanistic explanations for cellular immunity phenomena like anergy, peripheral tolerance, cell-mediated suppression, TCR antagonism, and thymic selection events.