title: A monoclonal antibody that recognizes the E domain of staphylococcal protein A.
abstract: Staphylococcal protein A (SpA) binds Fcγ and VH3 clan Fab domains of human and animal immunoglobulin (Ig) with each of its five Ig binding domains (IgBDs), thereby supporting Staphylococcus aureus escape from opsonophagocytic killing and suppressing adaptive B cell responses. The variant SpAKKAA cannot bind Ig yet retains antigenic properties that elicit SpA-neutralizing antibodies and disease protection in mice, whereas S. aureus infection or SpA-immunization cannot elicit neutralizing antibodies. As a test for this model, we analyzed here mAb 358A76, which was isolated from SpA-immunized mice. Unlike SpAKKAA-derived mAbs, mAb 358A76 binds only the first IgBD (E) but not any of the other four IgBDs (D-A-B-C) and its binding can neutralize only the E domain of SpA, which does not provide disease protection in mice. These results are in agreement with a model whereby wild-type SpA-immunization generates a limited antibody response without neutralizing and/or disease protective attributes.
authors.affiliation: Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
authors.forename: Hwan Keun
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
authors.forename: Carla
authors.initials: C
authors.lastname: Emolo
authors.affiliation: Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
authors.forename: Dominique
authors.initials: D
authors.lastname: Missiakas
authors.affiliation: Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA. Electronic address: oschnee@bsd.uchicago.edu.
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D013205:Staphylococcal Protein A / Q000276:immunology*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D013205:Staphylococcal Protein A
keywords: B Cell superantigen; Disease protection; Monoclonal antibody; Opsonophagocytic clearance; Staphylococcal protein A; Therapeutic vaccine