B lymphocytes are activated towards adapative immunity through integration of two signals: antigen binding to the B cell receptor (BCR) and the recruitment of T cell help. The BCR plays multiple roles in this process; mediating signal transduction upon antigen binding as well as presentation of antigen on MHC class II molecules (MHC-II). Identifying molecular interactions between antigen and the BCR that promote robust signal transduction and antigen presentation is essential for designing synthetic vaccines that can activate humoral immunity. Previously, we have shown that multivalent BCR ligand derived from ring-opening metathesis polymerization (ROMP) behaves as synthetic antigen: effectively clustering the BCR and activating B cell signaling. We have shown that by systematically altering ligand parameters, we can tune BCR signal output. We further hypothesized that a polymer scaffold bearing peptide cargo could be used to deliver antigen for presentation to CD4+ T cells. We have shown that such a scaffold is capable of both activating signaling through the BCR and delivering peptide for MHC-II presentation. Our data validates an in vitro system where antigen parameters can be systematically altered and the effect on both BCR signaling and antigen presentation can be quantitatively measured. Such a system will provide insight for designing synthetic vaccines that maximize the B cell immune response.

Investigating mechanisms of B cell antigen recognition with synthetic multivalent ligands

246th National Meeting (2013)

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