The B-cell epitopes indicated by the SPR experiments are visualized using space-filling depictions of the FVIII-C2 domain crystal structure in standard orientation, with the membrane-interacting loops pointing downward. The FVIII-C2 structure is also shown rotated 180° about the vertical axis for type AB and type B mAbs to visualize both sides of the molecule. The B-cell epitopes identified on the basis of altered binding kinetics are color-coded according to FVIII inhibitor type; that is, A (red/salmon), AB (orange/yellow), B (dark/light green), BC (dark/light blue), and C (dark/light magenta). The darker colors indicate residues for which amino acid substitutions increased the residence time by at least 10 times compared with that for WT-FVIII-C2 binding to this mAb. Substitutions abrogating binding were also colored darker. Substitutions for which accurate k_d values could not be obtained were not colored darker because their effects on kinetics may have been in part a result of effects on protein stability. Several outlier residues identified as candidates using the cutoff criterion of k_d(mutein) > 2.0 k_d(WT) are not shown, as they were eliminated after visualization of the FVIII-C2 crystal structure.