title: Regions of recognition by blocking antibodies on the light chain of botulinum neurotoxin A: antigenic structure of the entire toxin.
abstract: The continuous regions on botulinum neurotoxin A (BoNT/A) light (L) chain recognized by anti-toxin antibodies (Abs) from mouse, horse and chicken have been mapped. We synthesized a panel of thirty-two 19-residue peptides that overlapped consecutively by 5 residues and encompassed the entire L chain (residues 1-453). Mouse Abs recognized 5 major antigenic regions on the L chain, horse Abs recognized 9 while chicken Abs recognized 8 major antigenic regions. Overall, however, the three host species recognized, to some extent, similar, but not identical, peptides and the levels of Abs directed against a given region varied with the immunized host. Differences in the MHC of the host caused variation in levels of Ab recognition and some epitopes showed right or left frame-shifts among the species. Selected region(s) were also uniquely recognized by one species (e.g., peptide L1 by horse Abs). Mapping of the L chain antigenic regions and the previous localization of the regions on the H chain with the same antisera, has permitted description of the complete antigenic structure of BoNT/A. The locations in the 3-dimensional structure of the antigenic regions of the entire toxin are shown for mouse Abs. In the 3-D structure, the antigenic regions are on the surface of the toxin and when antibodies are bound the enzymatic activity of the light chain is obstructed.
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Behzod Z
authors.initials: BZ
authors.lastname: Dolimbek
authors.forename: Lance E
authors.initials: LE
authors.lastname: Steward
authors.forename: K Roger
authors.initials: KR
authors.lastname: Aoki
authors.forename: M Zouhair
authors.initials: MZ
authors.lastname: Atassi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D000918:Antibody Specificity / Q000276:immunology; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D019274:Botulinum Toxins, Type A / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D013045:Species Specificity
chemical_list: D019138:Antibodies, Blocking; D000941:Antigens; D010455:Peptides; D019274:Botulinum Toxins, Type A