Document Detail


Immunosuppression by co-stimulatory molecules: inhibition of CD2-CD48/CD58 interaction by peptides from CD2 to suppress progression of collagen-induced arthritis in mice.
MedLine Citation:
PMID:  23530775     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Targeting co-stimulatory molecules to modulate the immune response has been shown to have useful therapeutic effects for autoimmune diseases. Among the co-stimulatory molecules, CD2 and CD58 are very important in the early stages of generation of an immune response. Our goal was to utilize CD2-derived peptides to modulate protein-protein interactions between CD2 and CD58, thereby modulating the immune response. Several peptides were designed based on the structure of the CD58-binding domain of CD2 protein. Among the CD2-derived peptides, peptide 6 from the F and C β-strand region of CD2 protein exhibited inhibition of cell-cell adhesion in the nanomolar concentration range. Peptide 6 was evaluated for its ability to bind to CD58 in Caco-2 cells and to CD48 in T cells from rodents. A molecular model was proposed for binding a peptide to CD58 and CD48 using docking studies. Furthermore, in vivo studies were carried out to evaluate the therapeutic ability of the peptide to modulate the immune response in the collagen-induced arthritis (CIA) mouse model. In vivo studies indicated that peptide 6 was able to suppress the progression of CIA. Evaluation of the antigenicity of peptides in CIA and transgenic animal models indicated that this peptide is not immunogenic.
Authors:
Ameya Gokhale; Shanthi Kanthala; John Latendresse; Veena Taneja; Seetharama Satyanarayanajois
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemical biology & drug design     Volume:  82     ISSN:  1747-0285     ISO Abbreviation:  Chem Biol Drug Des     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-21     Completed Date:  2014-01-23     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  101262549     Medline TA:  Chem Biol Drug Des     Country:  England    
Other Details:
Languages:  eng     Pagination:  106-18     Citation Subset:  IM    
Copyright Information:
© 2013 John Wiley & Sons A/S.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antibodies / chemistry,  immunology
Antigens, CD / chemistry,  immunology,  metabolism*
Antigens, CD2 / chemistry,  metabolism*
Antigens, CD58 / chemistry,  immunology,  metabolism*
Arthritis, Experimental / drug therapy,  pathology
Binding Sites
Caco-2 Cells
Cell Adhesion / drug effects
Fluorescent Dyes
Humans
Immunosuppression
Jurkat Cells
Mice
Mice, Inbred DBA
Mice, Transgenic
Molecular Docking Simulation
Peptides, Cyclic / chemistry,  pharmacology,  therapeutic use
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Grant Support
ID/Acronym/Agency:
AI075262/AI/NIAID NIH HHS; R01 AI075262/AI/NIAID NIH HHS; R01 AR030752/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Antigens, CD; 0/Antigens, CD2; 0/Antigens, CD58; 0/CD48 antigen; 0/Fluorescent Dyes; 0/Peptides, Cyclic
Comments/Corrections

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