Increased reactivity to myelin oligodendrocyte glycoprotein peptides and epitope mapping in HLA DR2(15)+ multiple sclerosis.
Multiple sclerosis (MS) is a central nervous system-specific inflammatory and demyelinating disease where a myelin-directed autoimmune response is thought to be pathogenetically relevant. Myelin oligodendrocyte glycoprotein (MOG) is a surface-exposed minor myelin component that is a prime candidate autoantigen. We have investigated peripheral blood lymphocyte responses to synthetic 15-26 amino acids long overlapping MOG peptides in 20 MS patients and 14 healthy controls with the MS-associated HLA haplotype DR2(15). There were significantly increased responses, in terms of numbers of cells secreting IFN-gamma detected by Elispot in response to several MOG-derived peptides in the MS patients, but not the healthy controls. MOG peptide 63-87 evoked the strongest response, and the stimulatory property of this peptide was confirmed in additional DR2(15)+ MS patients where a peptide concentration-dependent proliferative response, which was inhibited by the addition of anti-HLA class II antibodies, was observed. This is the first work detailing putative immunodominant T cell epitopes of MOG in DR2(15)+ MS patients.
Wallström
E
E
Neuroimmunology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden. erik.wallstrom@cmm.ki.se
Khademi
M
M
Andersson
M
M
Weissert
R
R
Linington
C
C
Olsson
T
T
D000328:Adult; D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000276:immunology*; D002455:Cell Division; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015802:HLA-DR2 Antigen / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000138:chemical synthesis / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology
D000954:Antigens, Surface; D018984:Epitopes, T-Lymphocyte; D015802:HLA-DR2 Antigen; C571326:MOG protein, human; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides; D007371:Interferon-gamma