Differences between T-cell reactivities to major myelin protein-derived peptides in opticospinal and conventional forms of multiple sclerosis and healthy controls.
In Japanese, susceptibility to the conventional form of multiple sclerosis (C-MS) is associated with the HLA-DRB1*1501-DRB5*0101 haplotype while susceptibility to the opticospinal form of MS (OS-MS) is associated with HLA-DPA1*0202-DPB1*0501. To clarify the characteristics of T cells autoreactive to myelin proteins in each MS subtype, we established T-cell lines reactive to such myelin antigens as myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) from 5 of 10 OS-MS patients, 6 of 11 C-MS patients and 7 of 13 healthy controls (HCs), and T-cell epitopes and their restriction molecules were determined. We found that (a) intermolecular epitope spreading was found to be significantly more frequent in MS patients than in HCs (P=0.0128), (b) intramolecular epitope spreading also tended to occur more frequently in MS patients than in HCs (P=0.0584), (c) in OS-MS, HLA-DR-restricted and MOG-autoreactive T cells were more frequently established as compared with those reactive to MBP or PLP epitopes and (d) in C-MS, HLA-DQ-restricted and PLP-autoreactive T cells dominated those autoreactive to MBP or MOG epitopes. A DPB1*0501-restricted MBP-reactive T-cell clone from a patient with OS-MS provided evidence that the first HLA class II anchor amino acid of peptide bound to disease-susceptible DP5 molecule was distinct from that for the DR2 molecule. Taken together, these differences in specificities of myelin-autoreactive T cells between C-MS and OS-MS as well as the difference in the anchor motif of the binding peptides between each MS subtype-susceptible HLA class II molecule may contribute to the development of distinct clinical phenotypes.
Minohara
M
M
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ochi
H
H
Matsushita
S
S
Irie
A
A
Nishimura
Y
Y
Kira
J
J
D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000096:biosynthesis; D002999:Clone Cells; D018604:Epitope Mapping / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005260:Female; D006682:HLA-DP Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology*; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009900:Optic Nerve / Q000473:pathology*; D010446:Peptide Fragments / Q000276:immunology*; D013116:Spinal Cord / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; C571326:MOG protein, human; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments