Inhibition of experimental autoimmune encephalomyelitis in SJL mice by oral administration of retro-inverso derivative of encephalitogenic epitope P87-99

etro-inverso modification of peptides preserves parent peptide overall topo logy and provides at the same time stability to proteolysis, leading to der ivatives with prolonged half-life in vitro and in vivo. In this study the e ncephalitogenic epitope P87-99 Of myelin basic protein has been prepared in the retro-inverso form to examine its biological activity in a murine mode l 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 se lective T cell hyporesponsiveness, as measured by a reduction in the prolif erative response of lymph node T cells after antigen challenge. Oral admini stration of retro-inverso peptide decreased the disease severity significan tly and delayed considerably the disease onset in treated mice. Enhancement of resistance to proteolysis by retro-inverso modification of encephalitog enic epitopes may increase the therapeutic value of oral tolerance inductio n in the treatment of multiple sclerosis and other Th1-associated inflammat ory disorders.