Prevention of experimental autoimmune encephalomyelitis by encephalitogenic epitope sequence simplified derivatives.
The encephalitogenic epitope P81-100 from mouse myelin basic protein was used to generate two simplified derivatives with glycine substitutions in alternating positions which were tested for their biological activity in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis. While both derivatives were unable to induce in mice the disease at the same 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 different 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 protecting from the disease.
Marino
M
M
TECNOGEN S.C.p.A., Parco Scientifico, 81015 (CE), Piana di Monte Verna, Italy.
Ippolito
A
A
Ruvo
M
M
Scarallo
A
A
Volpe
S
S
Fassina
G
G
D000818:Animals; D000940:Antigenic Variation / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D000939:Epitopes / Q000276:immunology*; D005998:Glycine / Q000276:immunology; D006649:Histocompatibility Antigens; D007108:Immune Tolerance; D007167:Immunotherapy; D008213:Lymphocyte Activation; D051379:Mice; D009103:Multiple Sclerosis / Q000628:therapy; D004676:Myelin Basic Protein / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D013601:T-Lymphocytes
D000939:Epitopes; D006649:Histocompatibility Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C432789:myelin basic protein 81-100; D005998:Glycine