Multivalent Antigens for Promoting B and T Cell Activation

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens / chemistry
  • Antigens / immunology*
  • B-Lymphocytes / immunology*
  • Epitopes / chemistry
  • Epitopes / immunology
  • Humans
  • Interleukin-2 / immunology
  • Lymphocyte Activation*
  • Models, Molecular
  • Molecular Sequence Data
  • T-Lymphocytes / immunology*


  • Antigens
  • Epitopes
  • Interleukin-2