ANTIGENIC AND IMMUNOLOGICAL MIMICRY OF PEPTIDE MIMOTOPES OF LEWIS CARBOHYDRATE ANTIGENS

Peptides may substitute for carbohydrates in reactions with carbohydra te-specific molecules. Recently, we found that peptides containing aro matic residues mimic mucin and histo-blood group related carbohydrate epitopes, eliciting polyclonal responses crossreactive with bacterial and viral antigens that express these carbohydrate forms. These result s demonstrate that peptides can function in in vivo and in vitro model s as carbohydrate surrogate antigens, To further explore the nature of the antigenic and immunogenic properties of such mimotopes, synthetic peptides with aromatic amino acids were tested to delineate reactivit y patterns with several anti-neolactoseries monoclonal antibodies (MAb s). These MAbs recognize biologically important conformations of the h isto-blood group related Lewis antigens expressed on the surface of a variety of human cancers. Results by ELISA demonstrate that the MAbs c an distinguish particular peptide motifs that include the sequences GG IYYPYDIYYPYDIYYPYD, GGIYWRYDIYWRYDIYWRYD and GGIYYRYDIYYRYDIYYRYD. Sub stitution of Arg by Pro dimished the reactivity of the anti-Lewis Y (L eY) Mab BR55-2. Binding of LeY to BR55-2 was inhibitable by the Arg co ntaining peptides. Serum against all three peptides displayed reactivi ty with synthetic histo-blood group related antigen probes. Immunologi c presentation of the peptides as multiple antigen peptides (MAPs) imp roved peptide ability to induce LeY specific immune responses. Serum b ound to human tumor cells that preferentially expressed neolactoseries antigens, but not to normal tissues. Immunoprecipitation of human bre ast tumor cell lysates before and after treatment with tunicamycin con firmed serum carbohydrate binding. The anti-peptide sera mediated tumo r cell killing by complement mediated cytotoxicity. These results indi cate that mapping peptide epitopes with anti-carbohydrate antibodies c an lend to defining antibody fine specificities that can go undetected by screening of carbohydrate antigens alone. In addition, these resul ts confirm that peptides and carbohydrates can bind to the same antibo dy binding site and that peptides can structurally mimic salient featu res of carbohydrate epitopes. (C) 1998 Published by Elsevier Science L td. All rights reserved.