Mucosal tolerance in a murine model of experimental autoimmune encephalomyelitis.

Attempts to induce oral tolerance in a murine model of EAE with either the dominant T-cell epitope or whole protein have failed. These results may, in part, be due to the extraordinarily low affinity for class II MHC displayed by the dominant T-cell epitope. This belief is supported by experiments using a high-affinity analogue of the peptide that was capable of inducing tolerance at a high dose. By contrast, peptide inhalation has proven an effective route for induction of mucosal tolerance in this model. Most importantly, the inhalation of a single peptide could inhibit disease induced by the complex mixture of antigens found in whole myelin. Peptide inhalation was effective both before and after disease induction, and there was a positive correlation between affinity of class II binding and tolerogenicity of a panel of analogues of the N-terminal peptide of myelin basic protein.