Table 1.

Binding affinities of Fc variant antibodies for human Fc receptors

FcγRI
H131 FcγRIIa
R131 FcγRIIa
FcγRIIb
IIa/IIb ratio*
V158 FcγRIIIa
F158 FcγRIIIa
Kd (nmol/L)FoldKd (μmol/L)FoldKd (μmol/L)FoldKd (μmol/L)FoldH131R131Kd (μmol/L)FoldKd (μmol/L)Fold
Native IgG10.12 ± 0.02§1.00.85 ± 0.031.00.91 ± 0.101.02.3 ± 0.31.02.72.50.28 ± 0.031.01.0 ± 0.2**1.0
G236A0.86 ± 0.050.140.13 ± 0.016.50.161 ± 0.0035.72.0 ± 0.21.215120.30 ± 0.030.930.97 ± 0.131.0
I332E0.041 ± 0.0232.90.67 ± 0.021.30.52 ± 0.031.81.7 ± 0.11.42.53.30.052 ± 0.0075.40.14 ± 0.027.1
I332E/G236A0.12 ± 0.031.00.089 ± 0.0079.60.110 ± 0.0038.30.81 ± 0.042.89.17.40.095 ± 0.0123.00.16 ± 0.036.3
S239D/I332E0.020 ± 0.0166.00.23 ± 0.023.70.12 ± 0.027.60.17 ± 0.02140.741.40.016 ± 0.001180.030 ± 0.00633
S239D/I332E/G236A0.044 ± 0.0152.70.027 ± 0.007310.013 ± 0.006700.17 ± 0.02146.3130.023 ± 0.004120.032 ± 0.00831
fuc(-)0.12 ± 0.041.01.1 ± 0.10.770.40 ± 0.052.32.4 ± 0.80.962.26.00.018 ± 0.003160.098 ± 0.01610
  • * IIa/IIb ratio = Kd (FcγRIIa) / Kd (FcγRIIb) for the H131 (left) or R131 (right) FcγRIIa allotype.

  • Kds were obtained from global Langmuir fits of Biacore data (mean ± SD). Ka = 1 / Kd.

  • Fold = Kd (IgG1) / Kd (variant).

  • § Literature value for the binding of native IgG1 to FcγRI by Biacore is 0.110 nmol/L (46).

  • Literature values for the binding of native IgG1 to FcγRIIb by Biacore and calorimetry vary from 0.95 to 3.8 μmol/L (26, 47, 48).

  • Literature values for the binding of native IgG1 to V158 FcγRIIIa by Biacore and calorimetry vary from 0.21 to 0.75 μmol/L (9, 26, 49).

  • ** Literature values for the binding of native IgG1 to F158 FcγRIIIa by Biacore and calorimetry vary from 2.7 to 5.0 μmol/L (26, 49). The ratio of affinities for binding of native IgG1 to the two FcγRIIIa alleles (Kd [F158] / Kd [V158]) is 4 in the current study. Literature values for this ratio by Biacore and calorimetry vary from 5 to 7 (26, 49).