Characterization of lethal factor binding and cell receptor binding domains of protective antigen of Bacillus anthracis using monoclonal anti bodies

SF Little, JM Novak, JR Lowe, SH Leppla… - …, 1996 - microbiologyresearch.org
SF Little, JM Novak, JR Lowe, SH Leppla, Y Singh, KR Klimpel, BC Lidgerding…
Microbiology, 1996microbiologyresearch.org
Lethal toxin from Bacillus anthracisis composed of protective antigen (PA) and lethal factor
(LF). Anti-PA mAbs that neutralized lethal toxin activity, either in vivo or in vitro, identified
three non-overlapping antigenic regions on PA. Two distinct antigenic regions were
recognized by the four mAbs that neutralized lethal toxin activity by inhibiting the binding of
125I-LF to cell-bound PA. Mapping showed that one mAb, 1G3PA63, recognized an epitope
on a 17 IcDa fragment located between amino acid residues Ser-168 and Phe-314. The …
Lethal toxin from Bacillus anthracisis composed of protective antigen (PA) and lethal factor (LF). Anti-PA mAbs that neutralized lethal toxin activity, either in vivo or in vitro, identified three non-overlapping antigenic regions on PA. Two distinct antigenic regions were recognized by the four mAbs that neutralized lethal toxin activity by inhibiting the binding of 125I-LF to cell-bound PA. Mapping showed that one mAb, 1G3PA63, recognized an epitope on a 17 IcDa fragment located between amino acid residues Ser-168 and Phe-314. The three other mAbs, 2D3PA, 2D5PA and 10D2PA, recognized an epitope between amino acids Ile-581 and Asn-601. A single antigenic region was recognized by the three mAbs, 3B6PA, 14B7PA and 10E10PA63, that inhibited binding of 125I-PA to cells. This region was located between amino acids Asp-671 and lle-721. These results confirm previously defined functional domains of PA and suggest that LF may interact with two different sites on PA to form lethal toxin.
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