Inhibition of experimental autoimmune encephalomyelitis in SJL mice by oral administration of retro-inverso derivative of encephalitogenic epitope P87-99.
Retro-inverso modification of peptides preserves parent peptide overall topology and provides at the same time stability to proteolysis, leading to derivatives with prolonged half-life in vitro and in vivo. In this study the encephalitogenic epitope P87 - 99 of myelin basic protein has been prepared in the retro-inverso form to examine its biological activity in a murine model of multiple sclerosis. Experiments of in vivo T cell tolerance induction in SJL mice revealed that the retro-inverso peptide was able to induce a selective T cell hyporesponsiveness, as measured by a reduction in the proliferative response of lymphnode T cells after antigen challenge. Oral administration of retro-inverso peptide decreased the disease severity significantly and delayed considerably the disease onset in treated mice. Enhancement of resistance to proteolysis by retro-inverso modification of encephalitogenic epitopes may increase the therapeutic value of oral tolerance induction in the treatment of multiple sclerosis and other Th1-associated inflammatory disorders.
Marino
M
M
Biopharmaceuticals, TECNOGEN S.C.p.A., Science Park, Piana di Monte Verna, Italy.
Ippolito
A
A
Fassina
G
G
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D000939:Epitopes / Q000008:administration & dosage* / Q000737:chemistry; D007108:Immune Tolerance; D066298:In Vitro Techniques; D051379:Mice; D004676:Myelin Basic Protein / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments