Antibody and T cell recognition of the light chain of botulinum neurotoxin A in two high-responder mouse strains.
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.
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA. matassi@bcm.tmc.edu
M Zouhair
MZ
Atassi
Minako
M
Oshima
Behzod Z
BZ
Dolimbek
K Roger
KR
Aoki
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000737:chemistry / Q000276:immunology*; D019274:Botulinum Toxins, Type A / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D003014:Clostridium botulinum / Q000737:chemistry / Q000276:immunology; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007106:Immune Sera / Q000276:immunology; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011863:Radioimmunoassay; D013045:Species Specificity; D014121:Toxoids / Q000276:immunology
D000907:Antibodies, Bacterial; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007106:Immune Sera; D009498:Neurotoxins; D010446:Peptide Fragments; D014121:Toxoids; D019274:Botulinum Toxins, Type A