Molecular immune recognition of botulinum neurotoxin B. The light chain regions that bind human blocking antibodies from toxin-treated cervical dystonia patients. Antigenic structure of the entire BoNT/B molecule.

Abstract

We recently mapped the regions on the heavy (H) chain of botulinum neurotoxin, type B (BoNT/B) recognized by blocking antibodies (Abs) from cervical dystonia (CD) patients who develop immunoresistance during toxin treatment. Since blocking could also be effected by Abs directed against regions on the light (L) chain, we have mapped here the L chain, using the same 30 CD antisera. We synthesized, purified and characterized 32 19-residue L chain peptides that overlapped successively by 5 residues (peptide L32 overlapped with peptide N1 of the H chain by 12 residues). In a given patient, Abs against the L chain seemed less intense than those against H chain. Most sera recognized a limited set of L chain peptides. The levels of Abs against a given region varied with the patient, consistent with immune responses to each epitope being under separate MHC control. The peptides most frequently recognized were: L13, by 30 of 30 antisera (100%); L22, by 23 of 30 (76.67%); L19, by 15 of 30 (50.00%); L26, by 11 of 30 (36.70%); and L14, by 12 of 30 (40.00%). The activity of L14 probably derives from its overlap with L13. The levels of Ab binding decreased in the following order: L13 (residues 169-187), L22 (295-313), L19 (253-271), and L26 (351-369). Peptides L12 (155-173), L18 (239-257), L15 (197-215), L1 (1-19) and L23 (309-327) exhibited very low Ab binding. The remaining peptides had little or no Ab-binding activity. The antigenic regions are analyzed in terms of their three-dimensional locations and the enzyme active site. With the previous localization of the antigenic regions on the BoNT/B H chain, the human Ab recognition of the entire BoNT/B molecule is presented and compared to the recognition of BoNT/A by human blocking Abs.

• Authors: M Zouhair Atassi, Joseph Jankovic, Lance E Steward, K Roger Aoki, Behzod Z Dolimbek
• Journal: Immunobiology (Immunobiology) Vol. 217 Issue 1 Pg. 17-27 (Jan 2012) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 21962573 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011. Published by Elsevier GmbH.

Chemical References

• Antibodies, Bacterial
• Antibodies, Blocking
• Immune Sera
• Neurotoxins
• Peptide Fragments
• rimabotulinumtoxinB
• Botulinum Toxins
• Botulinum Toxins, Type A

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Bacterial (blood, chemistry, immunology)
• Antibodies, Blocking (blood, genetics, immunology)
• Binding Sites, Antibody (genetics, immunology)
• Botulinum Toxins (administration & dosage, blood, chemistry, immunology)
• Botulinum Toxins, Type A (blood, chemistry, immunology)
• Clostridium botulinum (chemistry, immunology)
• Epitope Mapping
• Humans
• Immune Sera (immunology)
• Immunity, Humoral
• Mice
• Mice, Inbred ICR
• Molecular Sequence Data
• Neurotoxins (administration & dosage, blood, chemistry, immunology)
• Peptide Fragments (chemistry, immunology, metabolism)
• Protein Binding (genetics, immunology)
• Torticollis (blood, drug therapy, genetics, immunology)
• Treatment Failure