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.
Muraro
P A
PA
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bldg. 10, Room 5B-16, National Institutes of Health, 10 Center Drive MSC1400, 20892, Bethesda, MD, USA. murarop@ninds.nih.gov
Kalbus
M
M
Afshar
G
G
McFarland
H F
HF
Martin
R
R
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000276:immunology*; D000328:Adult; D000954:Antigens, Surface / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*
D000954:Antigens, Surface; D006684:HLA-DR Antigens; D009185:Myelin Proteins; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases