We conclude that the processing of AQP4 by antigen presenting cells in Lewis rats produces a highly encephalitogenic AQP4 epitope (AQP4268–285), that T cells specific for this epitope are found in the immune repertoire of normal Lewis rats and can be readily expanded, and that AQP4268–285-specific T cells produce NMO-like lesions in the presence of NMO-IgG. This evidence concerns the gene AQP4 and neuromyelitis optica.