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    Antigen-Specific Blocking of CD4-Specific Immunological Synapse Formation Using BPI and Current Therapies for Autoimmune Diseases

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    Siahaan_2012.pdf (945.4Kb)
    Issue Date
    2012-07
    Author
    Manikwar, Prakash
    Kiptoo, Paul
    Badawi, Ahmed H.
    Büyüktimkin, Barlas
    Siahaan, Teruna J.
    Publisher
    Wiley
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
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    Abstract
    In this review, we discuss T-cell activation, etiology, and the current therapies of autoimmune diseases (i.e., MS, T1D, and RA). T-cells are activated upon interaction with antigen-presenting cells (APC) followed by a “bull’s eye”-like formation of the immunological synapse (IS) at the T-cell–APC interface. Although the various disease-modifying therapies developed so far have been shown to modulate the IS and thus help in the management of these diseases, they are also known to present some undesirable side effects. In this study, we describe a novel and selective way to suppress autoimmunity by using a bifunctional peptide inhibitor (BPI). BPI uses an intercellular adhesion molecule-1 (ICAM-1)-binding peptide to target antigenic peptides (e.g., proteolipid peptide, glutamic acid decarboxylase, and type II collagen) to the APC and therefore modulate the immune response. The central hypothesis is that BPI blocks the IS formation by simultaneously binding to major histocompatibility complex-II and ICAM-1 on the APC and selectively alters the activation of T cells from TH1 to Treg and/or TH2 phenotypes, leading to tolerance.
    Description
    This is the peer reviewed version of the following article: Manikwar, P., Kiptoo, P., Badawi, A. H., Büyüktimkin, B. and Siahaan, T. J. (2012), Antigen-specific blocking of CD4-Specific immunological synapse formation using BPI and current therapies for autoimmune diseases. Med Res Rev, 32: 727–764. doi:10.1002/med.20243, which has been published in final form at http://doi.org/10.1002/med.20243. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
    URI
    http://hdl.handle.net/1808/24568
    DOI
    https://doi.org/10.1002/med.20243
    Collections
    • Pharmaceutical Chemistry Scholarly Works [319]
    Citation
    Manikwar, P., Kiptoo, P., Badawi, A. H., Büyüktimkin, B. and Siahaan, T. J. (2012), Antigen-specific blocking of CD4-Specific immunological synapse formation using BPI and current therapies for autoimmune diseases. Med Res Rev, 32: 727–764. doi:10.1002/med.20243

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    KU Libraries
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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