MYELIN AUTOREACTIVITY IN MULTIPLE-SCLEROSIS - RECOGNITION OF MYELIN BASIC-PROTEIN IN THE CONTEXT OF HLA-DR2 PRODUCTS BY LYMPHOCYTES-T OF MULTIPLE-SCLEROSIS PATIENTS AND HEALTHY DONORS
MYELIN AUTOREACTIVITY IN MULTIPLE-SCLEROSIS - RECOGNITION OF MYELIN BASIC-PROTEIN IN THE CONTEXT OF HLA-DR2 PRODUCTS BY LYMPHOCYTES-T OF MULTIPLE-SCLEROSIS PATIENTS AND HEALTHY DONORS
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DOI：
10.1073/pnas.87.20.7968
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发表时间：
1990-10-01
影响因子：
11.1
通讯作者：
WEKERLE, H
中科院分区：
文献类型：
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作者：
PETTE, M;FUJITA, K;WEKERLE, H
从8例多发性硬化症(MS)患者和2例健康献血员的外周血中建立了20株人髓鞘碱性蛋白(HMBP)特异性T淋巴细胞株，其中7株受DR2Dw2单倍型DR2a基因产物的限制。四个T细胞系在DR2Dw2单倍型的DR2b产物的背景下识别hMBP。DR2b限制性T细胞反应仅在MS患者来源的T细胞系中可见。DR2a异源二聚体呈现的hMBP表位被映射到覆盖氨基酸残基1-44、76-91、131-145或139-153的多肽，并被映射到Arg130-Ala131上跨越凝血酶裂解键的区域。受DR2b限制的T细胞系识别氨基酸80-99和148-162中的表位。多肽139-153也是在人类白细胞抗原-DR1分子的背景下提出的。我们的数据显示，在MS患者中，DR2Dw2单倍型的DR2a和DR2b产物都是髓鞘自身抗原hMBP的限制性元件，(Ii)DR2a分子至少呈现五种不同的hMBP特异性T淋巴细胞表位，以及(Iii)来自个体捐赠者的抗hMBP T细胞株在其抗原特异性和对HLA的限制性方面可能存在差异。
A panel of 20 human myelin basic protein (hMBP)-specific T-lymphocyte lines was generated from the peripheral blood of eight multiple sclerosis (MS) patients and two healthy donors, most of them expressing the HLA-DR2 haplotype, which is associated with an increased susceptibility to MS. Using HLA-DR gene-transfected mouse L-cell lines as antigen-presenting cells, we established that of the 20 hMBP-specific T-lymphocyte lines, 7 were restricted by the DR2a gene products of the DR2Dw2 haplotype. Four T-cell lines recognized hMBP in the context of the DR2b products of the DR2Dw2 haplotype. DR2b-restricted T-cell responses were demonstrable only in T-cell lines derived from MS patients. The hMBP epitopes presented by the DR2a heterodimer were mapped to peptides covering amino acid residues 1-44, 76-91, 131-145, or 139-153 and to a region spanning the thrombin-cleaved bond at Arg130-Ala131. DR2b-restricted T-cell lines recognized epitopes within amino acids 80-99 and 148-162. Peptide 139-153 was also presented in the context of HLA-DR1 molecules. Our data show that (i) in MS patients both the DR2a and DR2b products of the DR2Dw2 haplotype function as restriction elements for the myelin autoantigen hMBP, (ii) the DR2a molecule presents at least five different epitopes to hMBP-specific T lymphocytes, and (iii) anti-hMBP T-cell lines derived from individual donors can differ in their antigen fine specifically as well as in their HLA restriction.