Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.69 (botulinum neurotoxin)
 1,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 2196 73

We investigated in two inbred mouse strains the submolecular recognition of botulinum neurotoxin type A (BoNT/A) by Abs (B cells) and by T lymphocytes. For mapping, we employed a set of overlapping synthetic peptides that encompassed the entire light (L) chain of BoNT/A. After 3 BoNT/A toxoid injections, BALB/c T cells responded in vitro to challenge by peptides L18 (residues 239-257), L23 (309-327), L27 (365-383), L29 (393-411), or L31 (421-439) and more weakly to peptides L3 (29-47), L9/L10 (113-145), L15 (197-215), L17 (225-243), or L26 (351-369). The other peptides stimulated little or no T cell responses. SJL mice mounted, after 3 BoNT/A injections, stronger T cell responses that were medium-to-strong to peptides L2/L3 (15-47), L10/L11 (127-159), L19 (253-271), or L23 (309-327) and low to peptides L17 (225-243), L21 (281-299), L27 (365-383), or L30/L31 (407-439). After 3 BoNT/A injections, BALB/c and SJL antisera protected mice against lethal BoNT/A doses, but displayed restricted epitope profiles compared to outbred (ICR) mice Abs. BALB/c Abs displayed medium-to-high binding to peptides L4/L5 (43-75), L10/L11 (127-159), L18 (239-257) or L27 (365-383). SJL Abs were high to peptides L4/L5 (43-75), L14 (183-201), L16 (211-229), or L18/L19 (239-271), and medium to peptides L10 (127-145), L11 (141-159), L12 (155-173) or L29 (393-411). The other peptides had little or no binding. Responses to each T cell or Ab epitope were under separate genetic control. T and B (antibody) cell recognition regions may coincide, but there were also regions recognized only by Abs or by T cells.
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PMID:Antibody and T cell recognition of the light chain of botulinum neurotoxin A in two high-responder mouse strains. 2201 45

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.
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PMID:Regions recognized on the light chain of botulinum neurotoxin type A by T lymphocytes of SJL and BALB/c mice primed with inactivated toxin. 2515 1