title: Homo-β-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-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.
authors: Molecular Science Laboratory, National Institute of Immunology, New Delhi-110067, India.
authors: Ravi
authors: R
authors: Kant
authors: Molecular Science Laboratory, National Institute of Immunology, New Delhi-110067, India.
authors: Shweta
authors: S
authors: Pasi
authors: Molecular Science Laboratory, National Institute of Immunology, New Delhi-110067, India.
authors: Avadhesha
authors: A
authors: Surolia
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D015802:HLA-DR2 Antigen / Q000378:metabolism; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D004676:Myelin Basic Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010455:Peptides / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000596:Amino Acids; D016207:Cytokines; D000939:Epitopes; D015802:HLA-DR2 Antigen; C000603129:J5 peptide; D004676:Myelin Basic Protein; D010455:Peptides; C000603130:S18 peptide; D015847:Interleukin-4
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