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 perspective 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 peptides compete with LeY, as demonstrated by enzyme-linked immunosorbent assay 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 Fucalpha(1-3) moiety of LeY. Molecular modeling indicates that the peptides adopt an extended turn conformation within the BR55-2 combining site, serving to overlap the peptides with the LeY spatial position. Peptide binding is associated with only minor changes in BR55-2, relative to the BR55-2-LeY complex. Anti-peptide serum distinguishes the Fucalpha(1-3) from the Fucalpha(1-4) linkage, therefore differentiating 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.
Luo
P
P
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Canziani
G
G
Cunto-Amesty
G
G
Kieber-Emmons
T
T
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000276:immunology*; D018604:Epitope Mapping; D006801:Humans; D006860:Hydrogen Bonding; D007983:Lewis Blood Group Antigens / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D017433:Protein Structure, Secondary; D012984:Software
D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D009844:Oligosaccharides; D010455:Peptides