TOPOLOGICAL MIMICRY OF CROSS-REACTING ENANTIOMERIC PEPTIDE ANTIGENS

Rabbit polyclonal antibodies against multimeric peptide antigens were found to cross-react to a significant extent with topologically relate d variants of the parent antigen, where the chirality of each amino ac id residue (inverse derivatives), or the peptide sequence orientation (retro derivatives), was inverted or where both modifications were sim ultaneously introduced (retro-inverso derivatives), AU peptide variant s displayed similar recognition properties for antibodies and similar dose-dependent inhibitory effects on the interaction between immobiliz ed parent antigen and corresponding antibodies, Importance of peptide side chain topology on antigenicity was evaluated analyzing the recogn ition properties of two sequence-simplified parent peptide variants, o ne lacking of the side chains in the sequence odd position and the oth er in even position. These two variants, prepared introducing glycine residues alternatively in the parent peptide sequence, were found to c ross-react to a significant extent with the original antibody raised a gainst the parent peptide, Analysis of molecular models of peptide ena ntiomeric variants in the elongated all-trans configuration suggested that the topological equivalence of alternating side chains could lead to the formation of similar recognition surfaces, thus mimicking the parent peptide antigenic structure.