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ACS Chem Biol. 2015 Aug 21;10(8):1817-24. doi: 10.1021/acschembio.5b00239. Epub 2015 Jun 2.

Multivalent Antigens for Promoting B and T Cell Activation.

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1
†Department of Chemistry, ‡Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.

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.

PMID:
25970017
PMCID:
PMC4669068
DOI:
10.1021/acschembio.5b00239
[Indexed for MEDLINE]
Free PMC Article

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