ESTIMATION OF MAXIMAL AFFINITIES BETWEEN T-CELL RECEPTORS AND MHC PEPTIDE COMPLEXES/

Recognition of peptide/MHC complexes by T-cell receptors (TCRs) is a c ritical step for T-cell activation. We studied T-cell activation as a function of this interaction using a mathematical model. Unlike other models analysing TCR-MHC/peptide interactions, this study takes into a ccount that both TCRs and MHC/peptide complexes are anchored in membra nes and not in solution. The proposed model quantitatively predicts se veral essential features of antigen-specific T-cell activation, includ ing the experimentally determined rate of TCR-downregulation during pe ptide-specific T-cell stimulation. In addition, the model offers an ex planation as to why the affinity of the TCR for MHC/peptide complexes is low in general and it correctly predicts the on-rates of the TCR-MH C/peptide interaction observed in different model systems. Thus, the p roposed model predicts key parameters of T-cell activation and offers an explanation for the surprisingly low affinity of the TCR for its an tigen. (C) 1998 Elsevier Science Ltd. All rights reserved.