Submolecular recognition of the C-terminal domain of the heavy chain of botulinum neurotoxin type A by T cells from toxin-treated cervical dystonia patients

Immunobiology. 2016 Apr;221(4):568-76. doi: 10.1016/j.imbio.2015.12.002. Epub 2015 Dec 8.

Abstract

We determined the T-cell proliferative responses of the peripheral blood lymphocytes (PBL) from 25 botulinum neurotoxin (BoNT)-treated patients to 31 overlapping synthetic peptides encompassing the C-terminal half (residues 855-1296) of BoNT/A heavy chain. Responses of PBL to HC peptides varied among patients. Samples from 14 patients treated solely with BoNT/A recognized 2-13 (average 6.4) peptides/sample at Z>3.0 level. Six peptide regions representing residues 855-873, 1023-1041, 1051-1069, 1093-1111, 1135-1153 and 1247-1265 were frequently recognized by 36-57% of these PBLs. Influence of treatment parameters on T-cell recognition of the peptides was also investigated.

Keywords: Botulinum neurotoxin type A; Cervical dystonia; H(C) domain; MHC control; T-cell epitopes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Botulinum Toxins, Type A / chemistry*
  • Botulinum Toxins, Type A / immunology
  • Botulinum Toxins, Type A / therapeutic use
  • Clostridium botulinum / chemistry*
  • Clostridium botulinum / immunology
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / chemistry*
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Peptides / immunology
  • Primary Cell Culture
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Alignment
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Torticollis / drug therapy*
  • Torticollis / immunology
  • Torticollis / pathology

Substances

  • Epitopes, T-Lymphocyte
  • Peptides
  • Botulinum Toxins, Type A