دورية أكاديمية
Soluble Antigen Arrays Displaying Mimotopes Direct the Response of Diabetogenic T Cells
| العنوان: | Soluble Antigen Arrays Displaying Mimotopes Direct the Response of Diabetogenic T Cells |
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| المؤلفون: | Leon, Martin A., Fite, Rebuma Firdessa, Ruffalo, Justin Kristopher, Pickens, Chad J., Sestak, Joshua Orion, Creusot, Remi J., Berkland, Cory |
| بيانات النشر: | American Chemical Society |
| سنة النشر: | 2019 |
| المجموعة: | The University of Kansas: KU ScholarWorks |
| الوصف: | This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Biology, 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/acschembio.9b00090Test. ; Type 1 diabetes (T1D) is an autoimmune disorder which develops when insulin-producing, pancreatic beta cells are destroyed by an aberrant immune response. Current therapies for T1D either treat symptoms or cause global immunosuppression, which leave patients at risk of developing long-term complications or vulnerable to foreign pathogens. Antigen-specific immunotherapies have emerged as a selective approach for autoimmune diseases by inducing tolerance while mitigating global immunosuppression. We previously reported SAgAs with multiple copies of a multiple sclerosis (MS) autoantigen grafted onto hyaluronic acid (HA) as an efficacious therapy in experimental autoimmune encephalomyelitis. While the immune response of MS is distinct from T1D, the mechanism of SAgAs was hypothesized to be similar and via induction of immune tolerance to diabetes antigens. We synthesized SAgAs composed of HA polymer backbone conjugated with multiple copies of the T1D autoantigen mimotope p79 using aminooxy chemistry (SAgAp79) or using copper-catalyzed alkyne-azide cycloaddition (cSAgAp79) chemistry. SAgAs constructed using the hydrolyzable aminooxy linkage, thus capable of releasing p79, exhibited physicochemical properties similar to the triazole linkage. Both SAgAp79 versions showed high specificity and efficacy in stimulating epitope-specific T cells. SAgAs can be taken up by most immune cell populations but do not induce their maturation, and conventional dendritic cells are responsible for the brunt of antigen presentation within splenocytes. cSAgAp79 was more stimulatory than SAgAp79 both in vitro and in vivo, an effect that was ascribed to the peptide modification rather than the type of linkage. In summary, we ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | Leon, M. A., Firdessa-Fite, R., Ruffalo, J. K., Pickens, C. J., Sestak, J. O., Creusot, R. J., & Berkland, C. (2019). Soluble Antigen Arrays Displaying Mimotopes Direct the Response of Diabetogenic T Cells. ACS chemical biology, 14(7), 1436–1448. https://doi.org/10.1021/acschembio.9b00090Test; http://hdl.handle.net/1808/30789Test; orcid:0000-0002-8992-6306; orcid:0000-0002-9346-938X; PMC7402076 |
| DOI: | 10.1021/acschembio.9b00090 |
| الإتاحة: | https://doi.org/10.1021/acschembio.9b00090Test http://hdl.handle.net/1808/30789Test |
| حقوق: | Copyright © 2019 American Chemical Society ; openAccess |
| رقم الانضمام: | edsbas.2B66B5F1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acschembio.9b00090 |
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