The sample was then loaded onto a HiTrap Protein G HP column (GE Healthcare), eluted in 0.1 M glycine-HCl (pH 3.0), and immediately neutralised with 0.1 M Tris (pH 8.0). The sample was exchanged into 100 mM phosphate (pH 6.4), 300 mM NaCl, 2 mM EDTA, 5 mM L-cysteine (pH 6.4), and 1.5 mM β-mercaptoethanol using PD-10 columns (GE Healthcare).
Antibody fragments were generated by addition of papain agarose (Sigma), and overnight incubation at 37°C. The papain agarose was removed by centrifugation, and the sample loaded onto a HiTrap Protein A HP column (GE Healthcare). The material that did not bind to the column was gel filtered on a Superdex 200 16/60 column (GE Healthcare) in 20 mM HEPES (pH 7.5) and 150 mM NaCl.