Diversity and Plasticity of Self Recognition during the Development of Multiple Sclerosis

Recent studies using murine animal model systems indicate that clinical progression of autoimmune disease may be due to the sequential accumulation of neoautoreactivity charac-terized by extensive plasticity of self recognition. In the present study, we addressed the question of whether a simi-lar paradigm of self recognition is implicated in the devel-opment of multiple sclerosis (MS), a demyelinating disease with a presumed autoimmune etiology. Our approach was to determine serial changes over a 12–18-mo period in re-sponse to an epitope-mapping series of 265 12-mer peptides of myelin proteolipid protein (PLP) by patients with iso-lated monosymptomatic demyelinating syndromes (IMDS), a group of distinct clinical disorders with variable rates of progression to MS. Our data showed that an extensive arra