Antibody and T cell recognition of the light chain of botulinum neurotoxin A in two high-responder mouse strains

Abstract

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.