T cell response to 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in multiple sclerosis patients

T cell responses targeting myelin antigens are possibly involved in the pathogenesis of demyelinating diseases, such as multiple sclerosis (MS). Little is known about human T cell responses to 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), the third most abundant myelin protein. We examined the primary peripheral T cell response to CNPase and characterized CNPase-specific CD4+ long-term T cell lines (TCL) from MS patients and healthy donors. The strongest primary responses were found in two MS patients with very active disease and were directed against CNP(343-373). We identified immunodominant epitope clusters in the regions CNP(343-373) and (356-388) that were recognized in the context of MS-associated HLA-DR2 and DR4 molecules. These data provide the immunological basis for further investigation of CNPase as a potential target self-antigen in MS.