Antigen Potency and Maximal Efficacy Reveal a Mechanism of Efficient T Cell Activation

Sci. Signal.  07 Jun 2011:
Vol. 4, Issue 176, pp. ra39
DOI: 10.1126/scisignal.2001430

You are currently viewing the editor's summary.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

Modeling T Cell Activation

The efficiency of T cell activation depends on the binding parameters of the interaction between T cell receptors (TCRs) and peptide-bound major histocompatibility complexes (pMHCs). Two models propose different explanations for the relationship between TCR-pMHC binding and T cell functionality. The “affinity model” suggests that the number of TCR-pMHC complexes at equilibrium, which is governed by the dissociation constant KD, is the main determinant, whereas the “productive hit rate model” suggests that T cell responses depend on productive TCR-pMHC interaction times, which depend on the off-rate, koff. Dushek et al. performed mathematical modeling to show that both models predicted a correlation between KD and antigen potency (as measured by the EC50), but that only the productive hit rate model predicted a correlation between the maximal efficiency of antigen-induced responses and koff. Predictions from the productive hit rate model were validated in experiments with T cell clones and a panel of pMHC variants. Improved understanding of TCR-pMHC binding has implications to enhance responsiveness in various immunotherapies.