Antibody recognition of a conformational epitope in a peptide antigen: Fv-peptide complex of an antibody fragment specific for the mutant EGF receptor, EGFRvIII

Epitope mapping studies and the determination of the structure to 1.8 Angst rom resolution have been carried out for the antigen-binding fragment MR1 i n complex with peptide antigen. MR1 is specific for the novel fusion juncti on of the mutant epidermal growth factor receptor EGFRvIII and has been rep orted to have a high degree of specificity for the mutant EGFRvIII over the wild-type EGF receptor. The structure of the complex shows that the peptid e antigen residue side-chains found by epitope mapping studies to be critic al for recognition are accommodated in pockets on the surface of the Fv. Ho wever, the most distinctive portion of the peptide antigen, the novel fusio n glycine residue, makes no contact to the Fv and does not contribute direc tly to the epitope. The specificity of MR1 lies in the ability of this glyc ine residue to assume the restricted conformation needed to form a type II' beta -hairpin turn more easily, and demonstrates that a peptide antigen ca n be used to generate a conformational epitope. (C) 2001 Academic Press.