HLA-DRB5*0101 and-DRB1*1501 expression in the multiple sclerosis-associated HLA-DR15 haplotype
HLA-DRB5*0101 and-DRB1*1501 expression in the multiple sclerosis-associated HLA-DR15 haplotype
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DOI：
10.1016/j.jneuroim.2005.04.027
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发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
Martin, R
中科院分区：
文献类型：
--
作者：
Prat, E;Tomaru, U;Martin, R
高加索人的HLA区域，特别是DR15单倍型（包含DRB1*1501和DRB5*0101两个DRB*基因，以及紧密相连的DQ等位基因DQA*0102和DQB1*0602，它们共同构成DQw6分子），显示出与多发性硬化症（MS）最强的遗传关联。在DR15单倍型中，两条β链HLA-DRB1*1501和-DRB5*0101共表达，导致两种不同的表面HLA-DR α - β异源二聚体DR2b和DR2a。然而，大多数先前的研究都集中在DRB1*1501上，DR2a和DR2b都可能通过抗原呈递到髓磷脂特异性T淋巴细胞而参与MS的发病。因此，我们分析了这两个DR15基因在各种抗原提呈细胞（APCs）、中枢神经系统和胸腺组织中的表达。DRB5*0101在所有细胞类型和组织中的转录水平均较高。两种HLA-DR异源二聚体在细胞表面均有显著表达，在不同APCs中表现出差异表达模式。在干扰素- γ和介素-4刺激后，它们也同样受到调节。最后，免疫组化实验表明这两种分子在胸腺组织中均有表达。我们的结果鼓励未来的研究，以调查这两个基因在ms发病机制中的潜在功能相关性(C) 2005 Elsevier B.V.版权所有。
The HLA region, and particularly the DR15 haplotype (containing the two DRB* genes DRB1*1501 and DRB5*0101 and the tightly linked DQ alleles DQA*0102 and DQB1*0602, which together form the DQw6 molecule) in Caucasians, shows the strongest genetic association with multiple sclerosis (MS). In the DR15 haplotype, two beta-chains HLA-DRB1*1501 and -DRB5*0101 are co-expressed resulting in two different surface HLA-DR alpha beta heterodimers, DR2b and DR2a. Most previous studies focused on DRB1*1501, however, both DR2a, and DR2b may contribute to MS pathogenesis via antigen presentation to myelin-specific T lymphocytes. We therefore analyzed the expression of the two DR15 genes in various antigen presenting cells (APCs), central nervous system and thymic tissues. Transcript levels were higher for DRB5*0101 in all cell types and tissues. Both HLA-DR heterodimers were expressed at significant levels on the cell surface, where they showed a differential expression pattern in different APCs. They were similarly regulated after stimulation with interferon-gamma and interieukin-4. Finally, immunohistochemistry experiments indicated that both molecules were expressed in thymic tissue. Our results encourage future research to investigate the potential functional relevance of both genes for the pathogenesis of MS. (C) 2005 Elsevier B.V. All rights reserved.