Submolecular recognition regions of the HNdomain of the heavy chain of botulinum neurotoxin type A by T cells from toxin-treated cervical dystonia patients.
We have recently reported the submolecular T-cell recognition profile of the C-terminal half (HC, residues 855-1296) of the heavy (H) chain of botulinum neurotoxin type A (BoNT/A) with peripheral blood lymphocytes (PBL) from 25 BoNT-treated cervical dystonia (CD) patients. In the current study, we describe the mapping of the T-cell responses of the patients to the N-terminal half (HN,residues 449-859) of the heavy chain by using 29 synthetic overlapping peptides encompassing the entire HNdomain of BoNT/A. The profiles of the T-cell responses to the peptides varied among the patients. Samples from 14 patients treated solely with BoNT/A recognized 1-9 (average 3.7) peptides/sample at Z>3.0 level. Three peptide regions representing residues 631-649, 659-677 and 743-761 were frequently recognized by 29-64% of the patients. In patients with positive anti-BoNT/A antibody responses the overall positive T cell responses to the HNpeptides were significantly increased compared to antibody-negative patients. Influence of treatment parameters on the T-cell recognition of the HNpeptides was also observed. The results were compared with those of previously identified HCregion.
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Minako
M
Oshima
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Philip
P
Deitiker
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Joseph
J
Jankovic
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: matassi@bcm.edu.
M Zouhair
MZ
Atassi
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019274:Botulinum Toxins, Type A / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D000072417:Protein Domains / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014103:Torticollis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D016896:Treatment Outcome
D010446:Peptide Fragments; D019274:Botulinum Toxins, Type A
Botulinum neurotoxin type A; Cervical dystonia; H(N) domain; MHC control; Synthetic peptides; T-cell epitopes