title: Alterations in immunodominance of Streptococcus mutans AgI/II: lessons learned from immunomodulatory antibodies.
abstract: Streptococcus mutans antigen I/II (AgI/II) has been widely studied as a candidate vaccine antigen against human dental caries. In this report we follow up on prior studies that indicated that anti-AgI/II immunomodulatory monoclonal antibodies (MAbs) exerted their effects by destabilizing the native protein structure and exposing cryptic epitopes. We show here that similar results can be obtained by immunizing mice with truncated polypeptides out of the context of an intra-molecular interaction that occurs within the full-length molecule and that appears to dampen the functional response against at least two important target epitopes. Putative T cell epitopes that influenced antibody specificity were identified immediately upstream of the alanine-rich repeat domain. Adherence inhibiting antibodies could be induced against two discrete domains of the protein, one corresponding to the central portion of the molecule and the other corresponding to the C-terminus.
authors.affiliation: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, United States.
authors.forename: Rebekah A
authors.initials: RA
authors.lastname: Robinette
authors.affiliation: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, United States.
authors.forename: Kyle P
authors.initials: KP
authors.lastname: Heim
authors.affiliation: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, United States.
authors.forename: Monika W
authors.initials: MW
authors.lastname: Oli
authors.affiliation: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, United States.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Crowley
authors.affiliation: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, United States.
authors.forename: William P
authors.initials: WP
authors.lastname: McArthur
authors.affiliation: Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, United States. Electronic address: jbrady@dental.ufl.edu.
authors.forename: L Jeannine
authors.initials: LJ
authors.lastname: Brady
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013295:Streptococcus mutans / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D022541:Streptococcal Vaccines
keywords: Immune complex; Immunodominance; Monoclonal antibody; Streptococcus; Vaccine design