Publications & Reports

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

Katsara M, Yuriev E, Ramsland PA, Deraos G, Tselios T, Matsoukas J, Apostolopoulos V
Immunology and Vaccine Laboratory, Burnet Institute (Austin campus), VIC, Australia.

Abstract

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-A(s)).

Publication

  • Journal: Molecular Immunology
  • Published: 01/08/2008
  • Volume: 45
  • Issue: 13
  • Pagination: 3661-3670