Multifunctional, Multivalent PIC Polymer Scaffolds for Targeting Antigen-Specific, Autoreactive B Cells
| Autor: | Hendy Kristyanto, Miles D. Holborough-Kerkvliet, Lianne Lelieveldt, Yvonne Bartels, Roel Hammink, Karin A. J. van Schie, Rene E. M. Toes, Kimberly M. Bonger, Hans Ulrich Scherer |
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| Rok vydání: | 2022 |
| Předmět: |
rheumatoid arthritis
Technology Materials Science Biomaterials polyisocyanopeptides B-Lymphocytes Science & Technology Polymers Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Materials Science cyclic-citrullinated peptide Biomedical Engineering Synthetic Organic Chemistry Autoantigens ACTIVATION Arthritis Rheumatoid Biomaterials SYNTHETIC DENDRITIC CELLS All institutes and research themes of the Radboud University Medical Center Humans Streptavidin CD22 Peptides anti-citrullinated protein antibodies Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] |
| Zdroj: | Acs Biomaterials Science & Engineering, 8, 1486-1493 Acs Biomaterials Science & Engineering, 8, 4, pp. 1486-1493 ACS biomaterials science & engineering |
| ISSN: | 2373-9878 |
| Popis: | 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. ispartof: ACS BIOMATERIALS SCIENCE & ENGINEERING vol:8 issue:4 pages:1486-1493 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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