Document Detail


Vaccinelike and prophylactic treatments of EAE with novel I-domain antigen conjugates (IDAC): targeting multiple antigenic peptides to APC.
MedLine Citation:
PMID:  23148513     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-NH(2) 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 iv or sc injections of IDAC in a prophylactic or a vaccinelike dosing schedule. IDAC-3 was better than IDAC-1 in suppressing and delaying the onset of EAE when delivered in prophylactic and vaccinelike manners. IDAC-3 also suppressed subsequent relapse of the disease. The production of IL-17 was lowered in the IDAC-3-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-3-treated mice. In conclusion, the I-domain can effectively deliver antigenic peptides in a vaccinelike or prophylactic manner for inducing immunotolerance in the EAE mouse model.
Authors:
Barlas Büyüktimkin; Prakash Manikwar; Paul K Kiptoo; Ahmed H Badawi; John M Stewart; Teruna J Siahaan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-29
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  10     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-08     Completed Date:  2013-09-19     Revised Date:  2014-01-16    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  297-306     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen-Presenting Cells / immunology
Antigens / immunology*,  pharmacology*
Cell Differentiation / immunology
Encephalomyelitis, Autoimmune, Experimental / immunology*,  prevention & control*
Female
Immunoconjugates / immunology,  pharmacology*
Intercellular Adhesion Molecule-1 / immunology
Interleukin-10 / immunology
Interleukin-17 / immunology
Mice
Myelin Proteolipid Protein / immunology
Peptides / immunology*
T-Lymphocytes, Regulatory / immunology
Grant Support
ID/Acronym/Agency:
NIGMS, T32-GM008359//PHS HHS; R01 AI063002/AI/NIAID NIH HHS; R01-AI-063002/AI/NIAID NIH HHS; R56 AI063002/AI/NIAID NIH HHS; R56-AI-063002/AI/NIAID NIH HHS; T32 GM008359/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens; 0/IL10 protein, mouse; 0/Immunoconjugates; 0/Interleukin-17; 0/Myelin Proteolipid Protein; 0/Peptides; 0/Plp1 protein, mouse; 126547-89-5/Intercellular Adhesion Molecule-1; 130068-27-8/Interleukin-10
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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