title: Regions recognized on the light chain of botulinum neurotoxin type A by T lymphocytes of SJL and BALB/c mice primed with inactivated toxin.
abstract: Lymph node cells (LNC) from SJL (H-2(s)) and BALB/c (H-2(d)) mice primed once with inactivated botulinum neurotoxin type A (BoNT/A) were examined for their T-cell responses to each of 32 synthetic overlapping peptides (19 residues each, L1-L32) that encompass the entire L chain (residues 1-448) of BoNT/A. LNC of SJL gave strong responses to 6 regions on, L2 (residues 15-23), L10/11/12 (127-173), L19 (253-271) and L21 (281-299), and moderate to weak responses to L9 (113-131), L14/15 (183-215) and L27 (365-383). In BALB/c, LNC gave a substantial T-cell response only against peptide L12 (residues 155-173), and responded very weakly to 9 other peptides. The results were compared with the recognition profiles determined previously in these two strains after multiple BoNT/A injections. Overall responses to the L-chain peptides of T cells in later profiles were found to be somewhat weakened in SJL and stayed essentially at a similar level in BALB/c, although responses to BoNT/A increased. In SJL, response to L10 (127-145) remained the highest in the later profile. Strong responses against L12 (155-173) observed in both strains at early stage were reduced to an insignificant level. Cross-reactivity to tetanus neurotoxin by BoNT/A-specific T cells was observed in SJL but not in BALB/c. Design of an effective synthetic peptide vaccine will require incorporation of both T cell- and Ab-recognition elements of the BoNT molecule. Significance and possible implications of these results on BoNT/A-specific T-cell responses of BoNT-treated patients are discussed.
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Minako
authors.initials: M
authors.lastname: Oshima
authors.affiliation: Allergan Inc., Irvine, CA 92612, USA.
authors.forename: K Roger
authors.initials: KR
authors.lastname: Aoki
authors.affiliation: 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.
authors.forename: M Zouhair
authors.initials: MZ
authors.lastname: Atassi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D019274:Botulinum Toxins, Type A
keywords: Botulinum neurotoxin type A; L chain; MHC control; Synthetic peptides; T cell epitopes; T cells