Mannosylation of mutated MBP83-99 peptides diverts immune responses from Th1 to Th2

Multiple sclerosis (MS) is an autoimmune demyelinating disease mediated primarily by CD4+ T cells. The design of peptide mutants of disease-associated myelin epitopes to alter immune responses offers a promising avenue for the treatment of MS. We designed and synthesized a number of peptide analogs...

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Main Authors: Katsara, M., Yuriev, E., Ramsland, Paul, Deraos, G., Tselios, T., Matsoukas, J., Apostolopoulos, V.
Format: Journal Article
Published: 2008
Online Access:http://hdl.handle.net/20.500.11937/47052
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author Katsara, M.
Yuriev, E.
Ramsland, Paul
Deraos, G.
Tselios, T.
Matsoukas, J.
Apostolopoulos, V.
author_facet Katsara, M.
Yuriev, E.
Ramsland, Paul
Deraos, G.
Tselios, T.
Matsoukas, J.
Apostolopoulos, V.
author_sort Katsara, M.
building Curtin Institutional Repository
collection Online Access
description Multiple sclerosis (MS) is an autoimmune demyelinating disease mediated primarily by CD4+ T cells. The design of peptide mutants of disease-associated myelin epitopes to alter immune responses offers a promising avenue for the treatment of MS. We designed and synthesized a number of peptide analogs by mutating the principal TCR contact residue based on MBP83-99 epitope and these peptides were conjugated to reduced mannan. Immune responses were diverted from Th1 to Th2 in SJL/J mice and generated antibodies which did not cross-react with native MBP protein. Peptide [Y91]MBP83-99 gave the best cytokine and antibody profile and constitutes a promising candidate peptide for immunotherapy of MS. Structural alignment of existing crystal structures revealed the peptide binding motif of I-As. Molecular modeling was used to identify H-bonding and van der Waals interactions between peptides and MHC (I-As). © 2008 Elsevier Ltd. All rights reserved.
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spelling curtin-20.500.11937-470522017-09-13T14:27:26Z Mannosylation of mutated MBP83-99 peptides diverts immune responses from Th1 to Th2 Katsara, M. Yuriev, E. Ramsland, Paul Deraos, G. Tselios, T. Matsoukas, J. Apostolopoulos, V. Multiple sclerosis (MS) is an autoimmune demyelinating disease mediated primarily by CD4+ T cells. The design of peptide mutants of disease-associated myelin epitopes to alter immune responses offers a promising avenue for the treatment of MS. We designed and synthesized a number of peptide analogs by mutating the principal TCR contact residue based on MBP83-99 epitope and these peptides were conjugated to reduced mannan. Immune responses were diverted from Th1 to Th2 in SJL/J mice and generated antibodies which did not cross-react with native MBP protein. Peptide [Y91]MBP83-99 gave the best cytokine and antibody profile and constitutes a promising candidate peptide for immunotherapy of MS. Structural alignment of existing crystal structures revealed the peptide binding motif of I-As. Molecular modeling was used to identify H-bonding and van der Waals interactions between peptides and MHC (I-As). © 2008 Elsevier Ltd. All rights reserved. 2008 Journal Article http://hdl.handle.net/20.500.11937/47052 10.1016/j.molimm.2008.04.024 restricted
spellingShingle Katsara, M.
Yuriev, E.
Ramsland, Paul
Deraos, G.
Tselios, T.
Matsoukas, J.
Apostolopoulos, V.
Mannosylation of mutated MBP83-99 peptides diverts immune responses from Th1 to Th2
title Mannosylation of mutated MBP83-99 peptides diverts immune responses from Th1 to Th2
title_full Mannosylation of mutated MBP83-99 peptides diverts immune responses from Th1 to Th2
title_fullStr Mannosylation of mutated MBP83-99 peptides diverts immune responses from Th1 to Th2
title_full_unstemmed Mannosylation of mutated MBP83-99 peptides diverts immune responses from Th1 to Th2
title_short Mannosylation of mutated MBP83-99 peptides diverts immune responses from Th1 to Th2
title_sort mannosylation of mutated mbp83-99 peptides diverts immune responses from th1 to th2
url http://hdl.handle.net/20.500.11937/47052