Vaccination, prevention,, and treatment of experimental autoimmune neuritis (EAN) by an oligomerized T cell epitope

Using a polypeptide oligomer harboring 16 repeats of the neuritogenic epito pe (aa 58-73) of myelin P2 protein separated by spacers, enhancement of the immune response to the P2 protein, an important neuritogenic autoantigen i n experimental autoimmune neuritis (EAN), was attempted. In contrast to a p revious study with PLP-16-mer antigen-specific response of T cells was atte nuated at all doses examined to a variable degree. Treatment of Lewis rats with the P2-16-mer up to 2 months before immunization with P2(53-78) (vacci nation) or after immunization but before appearance of disease (prevention) had a strong tolerizing effect against the induction of EAN on immunizatio n with P2(53-78). Moreover, rats injected with 200 mug of the P2-16-mer Lv. on day 11 after disease induction, at which time the initial signs of dise ase had appeared, were almost completely protected against progression of c linical disease, whereas animals treated with the same amount of monomeric control peptide developed severe disease (treatment). Similar results were obtained by Lv. treatment of adoptive-transfer EAN with the P2-16-mer. The lack of clinical signs of disease after 16-mer therapy could be correlated with a reduced proliferative response of P2(53-78)-specific lymph node cell s. The frequency of apoptotic T cells in sciatic nerve or in lymph node cel ls, however, was not increased by the 16-mer treatment, suggesting that ind uction of anergy or other forms of peripheral tolerance may be responsible for the effect. Thus, the oligomerized P2 peptide antigen was highly effect ive in all three treatment modalities examined in this specific autoreactiv e T cell-mediated immune response.