EXPLORING THE BASIS OF PEPTIDE-CARBOHYDRATE CROSS-REACTIVITY - EVIDENCE FOR DISCRIMINATION BY PEPTIDES BETWEEN CLOSELY-RELATED ANTICARBOHYDRATE ANTIBODIES

To investigate the molecular basis of antigenic mimicry by peptides, w e studied a pan el of closely related mAbs directed against the cell-w all polysaccharide of group A Streptacoccus. These antibodies have res tricted V-gene usage, indicating a shared mechanism of binding to a si ngle epitope, Epitope mapping studies using synthetic fragments of the cell-wall polysaccharide supported this conclusion. All of the mAbs i solated crossreactive peptides from a panel of phage-displayed librari es, and competition studies indicated that many of the peptides bind a t or near the carbohydrate binding site, Surprisingly, the peptides is olated by each mAb fell into distinct consensus-sequence groups that d iscriminated between the mAbs, and in general, the peptides bound only to the mAbs used for their isolation, Similar results were obtained w ith polyclonal antibodies directed against synthetic oligosaccharide f ragments of the streptococcal cell-wall polysaccharide. Thus, the pept ides appear to be specific for their isolating antibodies and art not recognized by the same mechanism as their carbohydrate counterparts.