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Microbiology 142 (1996), 707-715; DOI  10.1099/13500872-142-3-707
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Characterization of Lethal Factor Binding and Cell Receptor Binding Domains of Protective Antigen of Bacillus anthracis using Monoclonal Antibodies

Stephen F. Little1, Jeanne M. Novak1,{dagger}, John R. Lowe1, Stephen H. Leppla1,{ddagger},*, Yogendra Singh2,§, Kurt R. Klimpel2, Burton C. Lidgerding1,|| and Arthur M. Friedlander1

1US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA
2Laboratory of Microbial Ecology, National Institute of Dental Research, Bethesda, MD 20892, USA

* Author for correspondence: Stephen F. Little. Tel: +1 301 619 4914. Fax: +1 301 619 2152. e-mail: steve_little@ftdetrck-ccmail.army.mil

ABSTRACT

Lethal toxin from Bacillus anthracis is 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 kDa 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 Ile-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.

Keywords: Bacillus anthracis, protective antigen, epitope mapping

|| Present address: Shepherd College, Shepherdstown, WV 25443, USA

§ Present address: Centre for Biochemical Technology, Mall Road, Near Jubilee Hall, Delhi 110007, India.

{ddagger} Present address: Laboratory of Microbial Ecology, National Institute of Dental Research, Bethesda, MD 20892, USA.

{dagger} Present address: Division of Vaccines and Related Products Applications, FDA, 1401 Rockville Pike, Rockville, MD 20850-1448, USA.




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