dc.contributor.author | Griffin, J. Daniel | |
dc.contributor.author | Leon, Martin A. | |
dc.contributor.author | Salash, Jean R. | |
dc.contributor.author | Shao, Michael | |
dc.contributor.author | Hartwell, Brittany L. | |
dc.contributor.author | Pickens, Chad J. | |
dc.contributor.author | Sestak, Joshua O. | |
dc.contributor.author | Berkland, Cory | |
dc.date.accessioned | 2020-10-20T21:53:37Z | |
dc.date.available | 2020-10-20T21:53:37Z | |
dc.date.issued | 2019-04-17 | |
dc.identifier.citation | Griffin, J. D., Leon, M. A., Salash, J. R., Shao, M., Hartwell, B. L., Pickens, C. J., Sestak, J. O., & Berkland, C. (2019). Acute B-Cell Inhibition by Soluble Antigen Arrays Is Valency-Dependent and Predicts Immunomodulation in Splenocytes. Biomacromolecules, 20(5), 2115–2122. https://doi.org/10.1021/acs.biomac.9b00328 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/30793 | |
dc.description | This document is the Accepted Manuscript version of a Published Work that appeared in final form in
Biomacromolecules, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.biomac.9b00328. | en_US |
dc.description.abstract | Antigen valency plays a fundamental role in directing the nature of an immune response to be stimulatory or tolerogenic. Soluble Antigen Arrays (SAgAs) are an antigen-specific immunotherapy that combats autoimmunity through the multivalent display of autoantigen. While mechanistic studies have shown SAgAs to induce T and B-cell anergy, the effect of SAgA valency has never been experimentally tested. Here, SAgAs of discrete antigen valencies were synthesized by click chemistry and evaluated for acute B-cell signaling inhibition as well as downstream immunomodulatory effects in splenocytes. Initial studies using the Raji B-cell line demonstrated SAgA valency dictated the extent of calcium flux. Lower valency constructs elicited the largest reductions in B-cell activation. In splenocytes from mice with experimental autoimmune encephalomyelitis, the same valency-dependent effects were evident in the downregulation of the costimulatory marker CD86. The reduction of calcium flux observed in Raji B-cells correlated strongly with downregulation in splenocyte CD86 expression after 72 hours. Here, a thorough analysis of SAgA antigenic valency illustrates that low, but not monovalent, presentation of autoantigen was ideal for eliciting the most potent immunomodulatory effects. | en_US |
dc.description.sponsorship | Madison and Lila Self Graduate Fellowship at the University of Kansas | en_US |
dc.description.sponsorship | NIH T32 GM008545 | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | Copyright © 2019 American Chemical Society | en_US |
dc.subject | Soluble Antigen Array | en_US |
dc.subject | Antigen-Specific Immunotherapy | en_US |
dc.subject | Valency | en_US |
dc.subject | Calcium flux | en_US |
dc.subject | Anergy | en_US |
dc.subject | Click Chemistry | en_US |
dc.title | Acute B-Cell Inhibition by Soluble Antigen Arrays Is Valency-Dependent and Predicts Immunomodulation in Splenocytes | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Griffin, J. Daniel | |
kusw.kuauthor | Leon, Martin A. | |
kusw.kuauthor | Salash, Jean R. | |
kusw.kuauthor | Shao, Michael | |
kusw.kuauthor | Hartwell, Brittany L. | |
kusw.kuauthor | Pickens, Chad J. | |
kusw.kuauthor | Sestak, Joshua O. | |
kusw.kuauthor | Berkland, Cory | |
kusw.kudepartment | Bioengineering Graduate Program | en_US |
kusw.kudepartment | Chemistry | en_US |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
kusw.kudepartment | Chemical and Petroleum Engineering | en_US |
dc.identifier.doi | 10.1021/acs.biomac.9b00328 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-8316-6414 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-9346-938X | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC7402190 | en_US |
dc.rights.accessrights | openAccess | en_US |