A molecular basis for functional peptide mimicry of a carbohydrate antigen

Peptides may substitute for carbohydrate antigens in carbohydrate-specific immunological reactions. Using the recognition properties of an anti-Lewis Y (LeY) antibody, BR55-2, as a model system, we establish a molecular persp ective for peptide mimicry by comparing the three-dimensional basis of BR55 -2 binding to LeY with the binding of the same antibody to peptides, The pe ptides compete with LeY, as demonstrated by enzyme-linked immunosorbent ass ay and Biacore analysis. The computer program LUDI was used to epitope map the antibody-combining site, correlating peptide reactivity patterns. This approach identified amino acids interacting with the same BR55-2 functional residue groups that recognize the Fuc alpha(1-3) moiety of LeY. Molecular modeling indicates that the peptides adopt an extended turn conformation wi thin the BR55-2 combining site, serving to overlap the peptides with the Le Y spatial position. Peptide binding is associated with only minor changes i n BR55-2, relative to the BR55-2-LeY complex. Anti-peptide serum distinguis hes the Fuc alpha(1-3) from the Fuc alpha(1-4) linkage, therefore different iating difucosylated neolactoseries antigens, These results further confirm that peptides and carbohydrates can bind to the same antibody-binding site and that peptides can structurally and functionally mimic salient features of carbohydrate epitopes.