文章基本信息

标题：Homo-β-amino acid containing MBP(85–99) analogs alleviate experimental autoimmune encephalomyelitis
本地全文：下载
作者：Ravi Kant ; Shweta Pasi ; Avadhesha Surolia 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep08205
出版社：Springer Nature
摘要：MBP(85–99), an immuno-dominant epitope of myelin basic protein which binds to the major histocompatibility complex haplotype HLA-DR2 is widely implicated in the pathogenesis of multiple sclerosis. J5, an antagonist of MBP(85–99), that blocks the binding of MBP(85–99) to soluble HLA-DR2b much more efficiently than glatiramer acetate (a random copolymer comprising major MHC and T-cell receptor contact residues), was transformed into analogs with superior biological half-lives and antagonistic-activities by substitution of some of its residues with homo-β-amino acids. S18, the best analog obtained ameliorated symptoms of experimental autoimmune encephalomyelitis at least twice more effectively than glatiramer acetate or J5. S18 displayed marked resistance to proteolysis in-vitro ; biological impact of which was evident in the form of delayed clinical onset of disease and prolonged therapeutic-benefits. Besides active suppression of MBP(85–99)-reactive CD4⁺ T-cells in-vitro and in-vivo S18 treatment also generated IL-4 producing CD4⁺ T-cell clones, through which protective effect could be transferred passively.