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 related variants of the parent antigen, where the chirality of each amino acid residue (inverso derivatives), or the peptide sequence orientation (retro derivatives), was inverted or where both modifications were simultaneously introduced (retro-inverso derivatives). All peptide variants displayed similar recognition properties for antibodies and similar dose-dependent inhibitory effects on the interaction between immobilized parent antigen and corresponding antibodies. Importance of peptide side chain topology on antigenicity was evaluated analyzing the recognition properties of two sequence-simplified parent peptide variants, one lacking of the side chains in the sequence odd position and the other in even position. These two variants, prepared introducing glycine residues alternatively in the parent peptide sequence, were found to cross-react to a significant extent with the original antibody raised against the parent peptide. Analysis of molecular models of peptide enantiomeric 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.
Protein Engineering, Tecnogen S.C.p.A., Parco Scientifico, Piana di Monte Verna (CE), Italy.
A
A
Verdoliva
M
M
Ruvo
G
G
Cassani
G
G
Fassina
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000302:isolation & purification; D000937:Antigen-Antibody Reactions; D000941:Antigens / Q000276:immunology*; D002846:Chromatography, Affinity; D003429:Cross Reactions; D005998:Glycine; D007536:Isomerism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits / Q000276:immunology; D013237:Stereoisomerism
D000906:Antibodies; D000941:Antigens; D010455:Peptides; D005998:Glycine