The trouble arises when a new amino acid, together with surrounding residues, creates an allergenic peptide --a T-cell epitope--capable of triggering an immune response. Without a reliable way to predict T-cell epitopes, fixing proteins while avoiding allergic reactions requires the optimism of a high wire walker using a matchstick for a balance pole.
Now, a new technique may help engineers keep their footing. An in vitro cell-based assay,1 developed by Marcia Stickler, David Estell, and Fiona Harding, of Genencor International, of Palo Alto, Calif., lets protein engineers find out if changing an amino acid will bring an unwanted immune response. Genencor uses the assay to ensure that proteins developed for its personal care products won't cause allergic reaction; T-cell epitopes are systematically mapped, then, one by one, eliminated without sacrificing desirable protein traits. Developers of therapeutic proteins could do the same thing before going into clinical trials.
The assay tests ...
