WT | P257I/N434H | D376V/N434H | P257I/Q311I | |
---|---|---|---|---|
KDa (nM) | 209 ± 11 | 4.0 ± 0.7* | 4.0 ± 0.3* | 2.6 ± 0.5* |
kon (×106)(1/M · s) | 0.22 | 4.3 | 5.0 | 6.5 |
koff (×10-2)(1/s) | 4.6 | 1.7 | 2.0 | 1.7 |
t1/2b (min) | 0.25 | 0.68 | 0.58 | 0.68 |
pH50c | 6.3 ± 0.1 | 6.5 ± 0.1 | 6.3 ± 0.1 | 6.5 ± 0.2 |
% Bound pH 7.4d | 0.5 ± 3 | 10 ± 4 | 3 ± 1 | 7 ± 2 |
↵* P < 0.001 compared with WT.
↵ a KD data determined from kinetic analysis of two independent binding experiments and expressed as the mean ± S.D. (KD = koff/kon · 1 ×109).
↵ b Half-life of the IgG/FcRn complexes at pH 6.0 [t1/2 = (ln2/koff)/60].
↵ c pH at which 50% of the IgG/C-FcRn complexes dissociates as determined from a four-parameter nonlinear regression fit (described under Materials and Methods) of the ELISA data.
↵ d Percentage of the total antibody in preformed complexes that remained FcRn-bound at pH 7.4 as determined by ELISA.