MINIMAL REQUIREMENTS FOR PEPTIDE MEDIATED ACTIVATION OF CD8(+) CTL

A physical chemical model of T cell stimulation by class I-peptide com plexes was developed and used to analyse in vitro studies of gamma-int erferon release as a function of the number of peptide and MHC molecul es. The analysis provided reasonable estimates of well identified para meters, including equilibrium constants and the minimum number of T ce ll receptor-class I-peptide ternary complexes on a presenting cell req uired to activate T cells. The latter number was estimated as 3-5 per T cell. This is in distinct contrast to estimates in the literature of the number of peptide-MHC complexes required for activity, which is n ecessarily larger. The analysis also predicted that activity is potent iated by interaction between class I molecules, even if one member of the pair is not bound by antigen. The analytical approach used in this paper may be applicable to other activation systems.