Product Description | The immunodominant myelin basic protein (MBP) peptide comprising residues 87-99 is a self-antigen in multiple sclerosis (MS). Lys(91) and Pro(96) residues are important for encephalitogenicity. Replacement of Lys and/or Pro residues with Arg and/or Ala, respectively, results in suppression of experimental allergic encephalomyelitis (EAE). The potent linear altered peptide ligand of the immunodominant sequence MBP(87-99) may lead to the design of potent antagonist mimetics for treating MS. The altered peptide ligands (APLs) has a different topology, which could provide a possible mechanism of action for T-cell receptor (TCR) antagonism. Reference 1: DOI: 10.1021/jm0102147; Reference 2: DOI: 10.1016/j.jmgm.2007.02.004 |
Scientific Background | Myelin basic protein 87-99 is an immunodominant epitope recognised by T cells from multiple sclerosis patients and is presented by HLA-DR2, an allele associated with susceptibility to the disease. It has therefore been a focus for antigen-specific immunotherapy, where the aim is to blunt a defined autoreactive response rather than suppress immunity broadly. This product is the [Arg91, Ala96] substituted analogue, an altered peptide ligand of that epitope. Substituting the T-cell receptor contact residues of MBP87-99 changes how the peptide engages the receptor, and this particular analogue has been studied as an inhibitor of experimental autoimmune encephalomyelitis, with modelling work proposing a bioactive conformation to explain the change in behaviour. Related work has used molecular dynamics to compare the parent epitope with its antagonist analogues at the receptor level, and has examined how citrullination of these peptides shifts the response of patient-derived T cells toward a Th1 profile. |
References | 1. A putative bioactive conformation for the altered peptide ligand of myelin basic protein and inhibitor of experimental autoimmune encephalomyelitis [Arg91, Ala96] MBP87-99. Journal of Molecular Graphics and Modelling (2005). J Mol Graph Model 2005 2. Molecular dynamics at the receptor level of immunodominant myelin basic protein epitope 87-99 implicated in multiple sclerosis and its antagonists altered peptide ligands. (2007). PMID 17392002 3. Properties of myelin altered peptide ligand cyclo(87-99)(Ala91,Ala96)MBP87-99 render it a promising drug lead for immunotherapy of multiple sclerosis. cyclo(87-99) APL review |
