title: Characterization of lethal factor binding and cell receptor binding domains of protective antigen of Bacillus anthracis using monoclonal antibodies.
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.
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Little
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Novak
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Lowe
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Leppla
authors.affiliation: Laboratory of Microbial Ecology, National Institute of Dental Research, Bethesda, MD 20892, USA.
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Singh
authors.affiliation: Laboratory of Microbial Ecology, National Institute of Dental Research, Bethesda, MD 20892, USA.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Klimpel
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: Burton C
authors.initials: BC
authors.lastname: Lidgerding
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Friedlander
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D001483:Base Sequence; D001665:Binding Sites / Q000276:immunology; D018604:Epitope Mapping; D008969:Molecular Sequence Data
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin