ATTENTION: The software behind KU ScholarWorks is being upgraded to a new version. Starting July 15th, users will not be able to log in to the system, add items, nor make any changes until the new version is in place at the end of July. Searching for articles and opening files will continue to work while the system is being updated.
If you have any questions, please contact Marianne Reed at mreed@ku.edu .
Vaccine-like and Prophylactic Treatments of EAE with Novel IDomain Antigen Conjugates (IDAC): Targeting Multiple Antigenic Peptides to APC
dc.contributor.author | Büyüktimkin, Barlas | |
dc.contributor.author | Manikwar, Prakash | |
dc.contributor.author | Kiptoo, Paul | |
dc.contributor.author | Badawi, Ahmed H. | |
dc.contributor.author | Stewart, John M. | |
dc.contributor.author | Siahaan, Teruna J. | |
dc.date.accessioned | 2017-05-10T18:31:38Z | |
dc.date.available | 2017-05-10T18:31:38Z | |
dc.date.issued | 2013-01-07 | |
dc.identifier.citation | Büyüktimkin, B., Manikwar, P., Kiptoo, P. K., Badawi, A. H., Stewart, J. M., & Siahaan, T. J. (2013). Vaccine-like and Prophylactic Treatments of EAE with Novel I-Domain Antigen Conjugates (IDAC): Targeting Multiple Antigenic Peptides to APC. Molecular Pharmaceutics, 10(1), 297–306. http://doi.org/10.1021/mp300440x | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/24080 | |
dc.description.abstract | The objective of this work is to utilize novel I-domain antigenic-peptide conjugates (IDAC) for targeting antigenic peptides to antigen-presenting cells (APC) to simulate tolerance in experimental autoimmune encephalomyelitis (EAE). IDAC-1 and IDAC-3 molecules are conjugates between the I-domain protein and PLP-Cys and Ac-PLP-Cys-NH2 peptides, respectively, tethered to N-terminus and Lys residues on the I-domain. The hypothesis is that the I-domain protein binds to ICAM-1 and PLP peptide binds to MHC-II on the surface of APC; this binding event inhibits the formation of the immunological synapse at the APC-T-cell interface to alter T-cell differentiation from inflammatory to regulatory phenotypes. Conjugation of peptides to the I-domain did not change the secondary structure of IDAC molecules as determined by circular dichroism spectroscopy. The efficacies of IDAC-1 and -3 were evaluated in EAE mice by administering i.v or s.c. injections of IDAC in a prophylactic or a vaccine-like dosing schedule. IDAC-3 was better than IDAC-1 in suppressing and delaying the onset of EAE when delivered in prophylactic and vaccine-like manners. IDAC-3 also suppressed subsequent relapse of the disease. The production of IL-17 was lowered in the IDAC-33 treated mice compared to those treated with PBS. In contrast, the production of IL-10 was increased, suggesting that there is a shift from inflammatory to regulatory T-cell populations in IDAC-33treated mice. In conclusion, the Idomain can effectively deliver antigenic peptides in a vaccine-like or prophylactic manner for inducing immunotolerance in the EAE mouse model. | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/mp300440x. | en_US |
dc.subject | Multiple sclerosis | en_US |
dc.subject | EAE | en_US |
dc.subject | Vaccine | en_US |
dc.subject | Peptide/protein conjugates | en_US |
dc.subject | TCR/MHC-Ag | en_US |
dc.subject | PLP | en_US |
dc.subject | I-domain | en_US |
dc.subject | Multi-antigens | en_US |
dc.subject | Th1 | en_US |
dc.subject | Th17 | en_US |
dc.subject | T-reg | en_US |
dc.subject | APC | en_US |
dc.title | Vaccine-like and Prophylactic Treatments of EAE with Novel IDomain Antigen Conjugates (IDAC): Targeting Multiple Antigenic Peptides to APC | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Büyüktimkin, Barlas | |
kusw.kuauthor | Manikwar, Prakash | |
kusw.kuauthor | Kiptoo, Paul K. | |
kusw.kuauthor | Badawi, Ahmed H. | |
kusw.kuauthor | Stewart, John M. Jr. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1021/mp300440x | 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 | PMC3540176 | en_US |
dc.rights.accessrights | openAccess |