Figure 5.

Correlation of pMHC Potency with Effective Off Rates

(A) Model of TCR-pMHC confinement by rebinding. We used a mathematical model that accounted for a TCR-pMHC bound state (left), unbound but in physical proximity state (center), and a state where TCR and pMHC have moved apart (right). The rate of chemical dissociation is k_off and the rate of association is k^∗_on that is a first order rate, in units of s⁻¹, that depends on the macroscopic on rate k_on. When chemically dissociated (center), TCR-pMHC may move apart via diffusion or transport with a first order rate k₋. We propose that the potency of pMHC is governed by the amount of time it is confined to the TCR. The effective off rate to go from bound (left) to complete dissociation (right), given that potentially many rebinding events may take place, is given by k^∗_off = (k₋k_off)/(k^∗_on + k₋).

(B–G) The panels show fits of the confinement time (CT), molecular flexibility (MF), and the combined (CT+MF) models to the entire data set (B, D, F) or the subset of 13 pMHC variants (C, E, G). The abscissa represents the effective off rate from each model. In the case of the confinement time model, it is (b₂k_off)/(k_on + b₂), where b₂ is a fitted parameter. In the case of the molecular flexibility model, the abscissa is k_offexp(b₂ΔC_p), where b₂ is a fitted parameter. See Experimental Procedures for details on data fitting and representation of effective off rates.