Exploring the basis of peptide–carbohydrate crossreactivity: Evidence for discrimination by peptides between closely related anti-carbohydrate antibodies

• DOI: 10.1073/pnas.94.6.2454
• Publication Date: 2002-07-26T14:35:50Z
• Authors: Shannon L. Harris; Lisa Craig; Jarnail S. Mehroke; Michael Rashed; Michael B. Zwick; Kelly Kenar; Eric J. Toone; Neil Greenspan; France-Isabelle A...; José-R. Marino-Al...; B. Mario Pinto; Jamie K. Scott
• Keywords: 0301 basic medicine; Streptococcus pyogenes; Molecular Sequence Data; Polysaccharides, Bacterial; Antibodies, Monoclonal; Oligosaccharides; Enzyme-Linked Immunosorbent Assay; Cross Reactions; Shigella flexneri; Immunoglobulin kappa-Chains; 03 medical and health sciences; Carbohydrate Sequence; Immunoglobulin M; Antibody Specificity; Salmonella; Immunoglobulin G; Amino Acid Sequence; Peptides; Oligopeptides

To investigate the molecular basis of antigenic mimicry by peptides, we studied a panel of closely related mAbs directed against the cell-wall polysaccharide of group AStreptococcus. These antibodies have restrictedV-gene usage, indicating a shared mechanism of binding to a single epitope. Epitope mapping studies using synthetic fragments of the cell-wall polysaccharide supported this conclusion. All of the mAbs isolated crossreactive peptides from a panel of phage-displayed libraries, and competition studies indicated that many of the peptides bind at or near the carbohydrate binding site. Surprisingly, the peptides isolated by each mAb fell into distinct consensus-sequence groups that discriminated between the mAbs, and in general, the peptides bound only to the mAbs used for their isolation. Similar results were obtained with polyclonal antibodies directed against synthetic oligosaccharide fragments of the streptococcal cell-wall polysaccharide. Thus, the peptides appear to be specific for their isolating antibodies and are not recognized by the same mechanism as their carbohydrate counterparts.