Regions recognized on the light chain of botulinum neurotoxin type A by T lymphocytes of SJL and BALB/c mice primed with inactivated toxin |
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Authors: | Minako Oshima K. Roger Aoki M. Zouhair Atassi |
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Affiliation: | 1. Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA;2. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA;3. Allergan Inc., Irvine, CA 92612, USA |
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Abstract: | Lymph node cells (LNC) from SJL (H-2s) and BALB/c (H-2d) 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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Keywords: | Ab, antibody BoNT/A, botulinum neurotoxin type A BoNT/B, botulinum neurotoxin type B L chain, the light chain (residues 1&ndash 448) of BoNT/A LNC, lymph node cells HLA, human leukocyte antigen H chain, the heavy chain (residues 449&ndash 1296) of BoNT/A HN, N-terminal domain (residues 449&ndash 859) of H chain HC, C-terminal domain (residues 855&ndash 1296) of the H chain MHC, major histocompatibility complex PBL, peripheral blood lymphocytes PBS, 0.15 M NaCl in 0.01 M sodium phosphate buffer, pH 7.2 RIA, radioimmune assay SI, stimulation index (cpm of 3H-thymidine incorporated by antigen-stimulated T lymphocytes/cpm incorporated by unstimulated cells) TeNT, tetanus neurotoxin |
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