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Recognition of peptide/MHC complexes by T-cell receptors (TCRs) is a critical 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 account that both TCRs and MHC/peptide complexes are anchored in membranes and not in solution. The proposed model quantitatively predicts several essential features of antigen-specific T-cell activation, including the experimentally determined rate of TCR-downregulation during peptide-specific T-cell stimulation. In addition, the model offers an explanation 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-MHC/peptide interaction observed in different model systems. Thus, the proposed model predicts key parameters of T-cell activation and offers an explanation for the surprisingly low affinity of the TCR for its antigen.

Type

Journal article

Journal

Mol Immunol

Publication Date

02/1998

Volume

35

Pages

65 - 71

Keywords

Animals, Lymphocyte Activation, Major Histocompatibility Complex, Mice, Mice, Transgenic, Models, Biological, Models, Theoretical, Peptides, Receptors, Antigen, T-Cell, T-Lymphocytes