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.

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.

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