Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 447-456 |
| Number of pages | 10 |
| Journal | Tissue antigens |
| Volume | 57 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Jul 9 2001 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
- Biochemistry
- Genetics
Cite this
Differences between T-cell reactivities to major myelin protein-derived peptides in opticospinal and conventional forms of multiple sclerosis and healthy controls. / Minohara, M.; Ochi, H.; Matsushita, S.; Irie, A.; Nishimura, Y.; Kira, Jun-Ichi.
In: Tissue antigens, Vol. 57, No. 5, 09.07.2001, p. 447-456.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Differences between T-cell reactivities to major myelin protein-derived peptides in opticospinal and conventional forms of multiple sclerosis and healthy controls
AU - Minohara, M.
AU - Ochi, H.
AU - Matsushita, S.
AU - Irie, A.
AU - Nishimura, Y.
AU - Kira, Jun-Ichi
PY - 2001/7/9
Y1 - 2001/7/9
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0034960763&partnerID=8YFLogxK
U2 - 10.1034/j.1399-0039.2001.057005447.x
DO - 10.1034/j.1399-0039.2001.057005447.x
M3 - Article
C2 - 11556969
AN - SCOPUS:0034960763
VL - 57
SP - 447
EP - 456
JO - HLA
JF - HLA
SN - 2059-2302
IS - 5
ER -