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Homo-?-amino acid containing MBP(85-99) analogs alleviate experimental autoimmune encephalomyelitis.


ABSTRACT: 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-?-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.

SUBMITTER: Kant R 

PROVIDER: S-EPMC4314633 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Homo-β-amino acid containing MBP(85-99) analogs alleviate experimental autoimmune encephalomyelitis.

Kant Ravi R   Pasi Shweta S   Surolia Avadhesha A  

Scientific reports 20150203


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-acti  ...[more]

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