title: Constant domains influence binding of mouse-human chimeric antibodies to the capsular polypeptide of Bacillus anthracis.
abstract: Our laboratory previously described the binding characteristics of the murine IgG3 monoclonal antibody (MuAb) F26G3. This antibody binds the poly-glutamic acid capsule (PGA) of Bacillus anthracis, an essential virulence factor in the progression of anthrax. F26G3 IgG3 MuAb binds PGA with a relatively high functional affinity (10 nM), produces a distinct "rim" quellung reaction, and is protective in a murine model of pulmonary anthrax. This study engineered an IgG subclass family of F26G3 mouse-human chimeric antibodies (ChAb). The F26G3 ChAbs displayed 9- to 20-fold decreases in functional affinity, as compared with the parent IgG3 MuAb. Additionally, the quellung reactions that were produced by the ChAbs all differed from the parent IgG3 MuAb in that they appeared "puffy" in nature. This study demonstrates that human constant domains may influence multiple facets of antibody binding to microbial capsular antigens despite their spatial separation from the traditional antigen-binding site.
authors.affiliation: Department of Microbiology and Immunology; University of Nevada School of Medicine, Reno, NV, USA. daucoin@medicine.nevada.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hubbard
authors.forename: Peter
authors.initials: P
authors.lastname: Thorkildson
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kozel
authors.forename: David P
authors.initials: DP
authors.lastname: AuCoin
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology* / Q000382:microbiology; D000907:Antibodies, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D010455:Peptides / Q000276:immunology*; D017434:Protein Structure, Tertiary
chemical_list: D000907:Antibodies, Bacterial; D061067:Antibodies, Monoclonal, Humanized; D010455:Peptides
keywords: Bacillus anthracis; affinity; capsule; chimeric antibody; quellung reaction; spr