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    Altered peptide ligands of myelin basic protein (MBP87-99) conjugated to reduced mannan modulate immune responses in mice

    Access Status
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    Authors
    Katsara, M.
    Yuriev, E.
    Ramsland, Paul
    Tselios, T.
    Deraos, G.
    Lourbopoulos, A.
    Grigoriadis, N.
    Matsoukas, J.
    Apostolopoulos, V.
    Date
    2009
    Type
    Journal Article
    
    Metadata
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    Citation
    Katsara, M. and Yuriev, E. and Ramsland, P. and Tselios, T. and Deraos, G. and Lourbopoulos, A. and Grigoriadis, N. et al. 2009. Altered peptide ligands of myelin basic protein (MBP87-99) conjugated to reduced mannan modulate immune responses in mice. Immunology. 128 (4): pp. 521-533.
    Source Title
    Immunology
    DOI
    10.1111/j.1365-2567.2009.03137.x
    ISSN
    0019-2805
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/30761
    Collection
    • Curtin Research Publications
    Abstract

    Mutations of peptides to generate altered peptide ligands, capable of switching immune responses from T helper 1 (Th1) to T helper 2 (Th2), are promising candidates for the immunotherapy of autoimmune diseases such as multiple sclerosis (MS). We synthesized two mutant peptides from myelin basic protein 87-99 (MBP87-99), an immunodominant peptide epitope identified in MS. Mutations of residues K91 and P96, known to be critical T-cell receptor (TCR) contact sites, resulted in the mutant peptides [R91, A96]MBP87-99 and [A 91, A96]MBP87-99. Immunization of mice with these altered peptide ligands emulsified in complete Freund's adjuvant induced both interferon-? (IFN-?) and interleukin-4 (IL-4) responses compared with only IFN-? responses induced to the native MBP 87-99 peptide. It was of interest that [R91, A 96]MBP87-99 conjugated to reduced mannan induced 70% less IFN-? compared with the native MBP87-99 peptide. However, [A91, A96]MBP87-99 conjugated to reduced mannan did not induce IFN-?-secreting T cells, but elicited very high levels of interleukin-4 (IL-4). Furthermore, antibodies generated to [A91, A96]MBP87-99 peptide conjugated to reduced mannan did not cross-react with the native MBP87-99 peptide. By molecular modelling of the mutant peptides in complex with major histocompatibility complex (MHC) class II, I-As, novel interactions were noted. It is clear that the double-mutant peptide analogue [A91, A96]MBP 87-99 conjugated to reduced mannan is able to divert immune responses from Th1 to Th2 and is a promising mutant peptide analogue for use in studies investigating potential treatments for MS. © 2009 Blackwell Publishing Ltd.

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