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-DRBL*1501-DR55*0101 haplotype while susce ptibility to the opticospinal form of MS (OS-MS) is associated with HLA-DPA 1*0202-DPB1*0501. To clarify the characteristics of T cells autoreactive to myelin proteins in each MS subtype, we established T-cell lines reactive t o such myelin antigens as myelin basic protein (MBP), proteolipid protein ( PLP) and myelin oligodendrocyte glycoprotein (MOG) from 5 of 10 OS-MS patie nts, 6 of 11 C-MS patients and 7 of 13 healthy controls (HCs), and T-cell e pitopes and their restriction molecules were determined. We found that (a) intermolecular epitope spreading was found to be significantly more frequen t in MS patients than in HCs (P=0.0128), (b) intramolecular epitope spreadi ng also tended to occur more frequently in MS patients than in HCs (P=0.058 4), (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 epitop es and (d) in C-MS. HLA-DQ-restricted and PLP-autoreactive T cells dominate d those autoreactive to MBP or MOG epitopes, A DPB1*0501-restricted MBP-rea ctive T-cell clone from a patient with OS-MS provided evidence that the fir st HLA class II anchor amino acid of peptide bound to disease-susceptible D P5 molecule was distinct from that for the DR2 molecule. Taken together, th ese differences in specificities of myelin-autoreactive T cells between C-M S and OS-MS as well as the difference in the anchor motif of the binding pe ptides between each MS subtype-susceptible HLA class II molecule may contri bute to the development of distinct clinical phenotypes.