Prevention of experimental autoimmune encephalomyelitis by encephalitogenic epitope sequence simplified derivatives

The encephalitogenic epitope P81-100 from mouse myelin basic protein was us ed to generate two simplified derivatives with glycine substitutions in alt ernating positions which were tested for their biological activity in a mur ine model of multiple sclerosis, experimental autoimmune encephalomyelitis. While both derivatives were unable to induce in mice the disease at the sa me parent peptide P81-100 dosage. T cell proliferation assays demonstrated their ability to compete with the parental peptide in a dose related manner . Experiments of cell surface binding and T cell tolerance revealed a diffe rent behavior of the two derivatives, suggesting different roles in the MHC blockade or T cell tolerance. On induction of encephalomyelitis in animals by P81-100 treatment, one variant proved in vivo to be very effective in p rotecting from the disease. (C) 2001 Elsevier Science Ltd. All rights reser ved.