Estimation of maximal affinities between T-cell receptors and MHC/peptide complexes.
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.
Salzmann
M
M
Basel Institute for Immunology, Switzerland.
Bachmann
M F
MF
D000818:Animals; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008962:Models, Theoretical; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D010455:Peptides; D011948:Receptors, Antigen, T-Cell