DISPLAY-INDUCED ANTIGENIC VARIATION IN RECOMBINANT PEPTIDES

Peptide display on solvent-exposed surfaces of carrier proteins is a p romising approach pursuing the identification and improvement of react ive amino acid sequences. However, the contribution of the molecular e nvironment where the peptide is inserted on its interactive properties remains essentially unexplored. Ey an exhaustive antigenic analysis o f the same peptide displayed on 20 structurally distinct frameworks, w e show that peptide accommodation into the acceptor site has dramatic effects on its immunoreactivity. Conformational constraints can modula te the molecular recognition properties of the insert within a surpris ingly wide range, probably by affecting the positioning of critical co ntact residues. The observed display-induced antigenic variation promp ts a careful consideration of the molecular context when evaluating ou tput amino acid sequences from screening of peptide libraries or appli cation of directed molecular evolution technologies. (C) 1998 Academic Press.