title: Multivalent Antigens for Promoting B and T Cell Activation.
abstract: Efficacious vaccines require antigens that elicit productive immune system activation. Antigens that afford robust antibody production activate both B and T cells. Elucidating the antigen properties that enhance B-T cell communication is difficult with traditional antigens. We therefore used ring-opening metathesis polymerization to access chemically defined, multivalent antigens containing both B and T cell epitopes to explore how antigen structure impacts B cell and T cell activation and communication. The bifunctional antigens were designed so that the backbone substitution level of each antigenic epitope could be quantified using (19)F NMR. The T cell peptide epitope was appended so that it could be liberated in B cells via the action of the endosomal protease cathepsin D, and this design feature was critical for T cell activation. Antigens with high BCR epitope valency induce greater BCR-mediated internalization and T cell activation than did low valency antigens, and these high-valency polymeric antigens were superior to protein antigens. We anticipate that these findings can guide the design of more effective vaccines.
authors.affiliation: †Department of Chemistry, ‡Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Nitasha R
authors.initials: NR
authors.lastname: Bennett
authors.affiliation: †Department of Chemistry, ‡Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Zwick
authors.affiliation: †Department of Chemistry, ‡Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Adam H
authors.initials: AH
authors.lastname: Courtney
authors.affiliation: †Department of Chemistry, ‡Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Kiessling
mesh_terms: D000595:Amino Acid Sequence; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D000939:Epitopes; D007376:Interleukin-2