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Multifunctional, Multivalent PIC Polymer Scaffolds for Targeting Antigen-Specific, Autoreactive B Cells
[Image: see text] 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 immu...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006213/ https://www.ncbi.nlm.nih.gov/pubmed/35259296 http://dx.doi.org/10.1021/acsbiomaterials.1c01395 |
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author | 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 |
author_facet | 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 |
author_sort | Kristyanto, Hendy |
collection | PubMed |
description | [Image: see text] 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. |
format | Online Article Text |
id | pubmed-9006213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-90062132022-04-13 Multifunctional, Multivalent PIC Polymer Scaffolds for Targeting Antigen-Specific, Autoreactive B Cells 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 ACS Biomater Sci Eng [Image: see text] 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. American Chemical Society 2022-03-08 2022-04-11 /pmc/articles/PMC9006213/ /pubmed/35259296 http://dx.doi.org/10.1021/acsbiomaterials.1c01395 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | 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 Multifunctional, Multivalent PIC Polymer Scaffolds for Targeting Antigen-Specific, Autoreactive B Cells |
title | Multifunctional, Multivalent PIC Polymer Scaffolds
for Targeting Antigen-Specific, Autoreactive B Cells |
title_full | Multifunctional, Multivalent PIC Polymer Scaffolds
for Targeting Antigen-Specific, Autoreactive B Cells |
title_fullStr | Multifunctional, Multivalent PIC Polymer Scaffolds
for Targeting Antigen-Specific, Autoreactive B Cells |
title_full_unstemmed | Multifunctional, Multivalent PIC Polymer Scaffolds
for Targeting Antigen-Specific, Autoreactive B Cells |
title_short | Multifunctional, Multivalent PIC Polymer Scaffolds
for Targeting Antigen-Specific, Autoreactive B Cells |
title_sort | multifunctional, multivalent pic polymer scaffolds
for targeting antigen-specific, autoreactive b cells |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006213/ https://www.ncbi.nlm.nih.gov/pubmed/35259296 http://dx.doi.org/10.1021/acsbiomaterials.1c01395 |
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