Localization of the regions on the C-terminal domain of the heavy chain of botulinum toxin a recognized by t lymphocytes and by antibodies after immunization of mice with pentavalent toxoid
| Autor: | M. Z. Atassi, Middlebrook Jl, J S Rosenberg |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
T-Lymphocytes
Molecular Sequence Data Immunology Stimulation Peptide Lymphocyte Activation Botulinum toxin a Mice Clostridium botulinum Animals Amino Acid Sequence Botulinum Toxins Type A chemistry.chemical_classification Mice Inbred BALB C Heavy chain biology Chemistry C-terminus Toxoid General Medicine Toxoids Antibodies Bacterial Virology Peptide Fragments Immunization Bacterial Vaccines biology.protein Female Antibody Epitope Mapping |
| Zdroj: | Immunological Investigations. 26:491-504 |
| ISSN: | 1532-4311 0882-0139 |
| Popis: | We have mapped the regions recognized by T and/or B cells (Abs) on the C-terminal domain (Hc) of the heavy chain of botulinum neurotoxin serotype A (BoNT/A) after immunization of two inbred mouse strains with pentavalent toxoid (BoNTs A, B, C, D and E). Using a set of synthetic overlapping peptides, encompassing the entire Hc domain (residues 855-1296), we demonstrated that T cells of Balb/c (H-2d) mice, primed with one injection of toxoid, recognized two major regions within residues 897-915 and 939-957. After multiple inoculations with toxoid, T cells of Balb/c expanded their recognition ability and responded very well to challenge with peptide 1261-1279 and moderately to stimulation with peptide 1149-1167. Unlike Balb/c T cells, those of toxoid-primed SJL (H-2s) mice exhibited a more complex profile and responded to challenge with a large number of overlapping peptides. After one toxoid injection, however, three peptides, 897-915, 939-957/953-971 overlap and 1051-1069, were the most potent T cells stimulators. After three toxoid injections, peptides 897-915 and 1051-1069 remained immunodominant while the third region was shifted upstream to 925-943/939-957 overlap. The immunodominant epitope within peptide 897-915 was recognized exclusively by T cells, since no Abs were detected against this region. The Ab binding profiles of the two mouse strains were quite similar, showing only small quantitative differences. Both, Balb/c and SJL anti-toxoid Abs displayed strong binding mainly to peptide 1177-1195, followed by peptides 869-887/883-901 overlap and 1275-1296. In addition, a significant amount of Balb/c anti-toxoid Abs was bound to peptide 1135-1153. Unlike Balb/c Abs, that interacted weakly with peptides 995-1013 and 1051-1069, the anti-toxoid Abs of SJL mice exhibited strong binding toward both peptides. The results showed that, in a given strain, the regions recognized by anti-toxoid Abs and T cells may coincide or may be uniquely B or T cell determinants. |
| Databáze: | OpenAIRE |
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