Multifunctional, Multivalent PIC Polymer Scaffolds for Targeting Antigen-Specific, Autoreactive B Cells

Multivalent scaffolds that carry multiple molecules with immunophenotyping or immunomodulatory properties are invaluable tools for studying and modulating specific functions of human immune responses. So far, streptavidin–biotin-based tetramers have been widely used for B-cell immunophenotyping purp...

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Published in:ACS biomaterials science & engineering 2022-04, Vol.8 (4), p.1486-1493
Main Authors: Kristyanto, Hendy, Holborough-Kerkvliet, Miles D, Lelieveldt, Lianne, Bartels, Yvonne, Hammink, Roel, van Schie, Karin A. J, Toes, Rene E. M, Bonger, Kimberly M, Scherer, Hans Ulrich
Format: Article
Language:English
Subjects:
Arthritis, Rheumatoid
Autoantigens
B-Lymphocytes
Bio-interactions and Biocompatibility
Humans
Peptides
Polymers
Streptavidin
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Summary:Multivalent scaffolds that carry multiple molecules with immunophenotyping or immunomodulatory properties are invaluable tools for studying and modulating specific functions of human immune responses. So far, streptavidin–biotin-based tetramers have been widely used for B-cell immunophenotyping purposes. However, the utility of these tetramers is limited by their tetravalency, the inherent immunogenicity of streptavidin (a bacterial protein that can potentially be recognized by B cells), and the limited feasibility to functionalize these reagents. This has rendered tetramers suboptimal for studying rare, in particular, antigen-specific B-cell populations in the context of clinical applications. Here, we used polyisocyanopeptides (PICs), multivalent polymeric scaffolds functionalized with around 50 peptide antigens, to detect autoreactive B cells in the peripheral blood of patients with rheumatoid arthritis. To explore the potential immunomodulatory functionalities, we functionalized PICs with autoantigenic peptides and a trisaccharide CD22 ligand to inhibit autoreactive B-cell activation through interference with the B-cell receptor activation pathway, as evidenced by reduced phospho-Syk expression upon PIC binding. Given the possibilities to functionalize PICs, our data demonstrate that the modular and versatile character of PIC scaffolds makes them promising candidates for future clinical applications in B-cell-mediated diseases.
ISSN:2373-9878
2373-9878
DOI:10.1021/acsbiomaterials.1c01395