Association of ankylosing spondylitis with HLA-B27 and ERAP1: Pathogenic role of antigenic peptide
Association of ankylosing spondylitis with HLA-B27 and ERAP1: Pathogenic role of antigenic peptide
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DOI：
10.1016/j.mehy.2012.10.003
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发表时间：
2013-01-01
影响因子：
4.7
通讯作者：
Xu, Weidong
中科院分区：
文献类型：
--
作者：
Chen, Bin;Li, Dahe;Xu, Weidong
强直性脊柱炎（AS）是一种血清阴性的炎性关节炎，其与人类白细胞抗原（HLA）-B27的强烈遗传关联已被发现近40年。然而，其机制仍然知之甚少。近年来，随着遗传学的发展，越来越多的基因被发现与该病密切相关。全基因组关联研究确定了AS和ERAP 1（内质网相关氨肽酶1）之间的关联。ERAP 1在将抗原肽修剪至最佳长度以结合ER（内质网）中的HLA-B27方面显示出潜力。然而，在肽的转运、加工和呈现过程中，肽的长度受到严格限制。提出了AS的异常机制可能与ER抗原前体N端序列的修剪和呈递给T细胞受体的抗原肽长度有关的假说。(C)2012爱思唯尔有限公司保留所有权利。
Ankylosing spondylitis (AS) is a form of seronegative inflammatory arthritis whose strong genetic association with the human leucocyte antigen (HLA)-B27 has been known for almost 4 decades. However, its mechanism remains poorly understood. Recently, with the development of genetics, further more genes have been robustly associated with the disease. Genome-wide association studies identified the association between AS and ERAP1 (endoplasmic reticulum associated aminopeptidase 1). And ERAP1 has shown the potential in trimming antigenic peptides to optimal length for binding to HLA-B27 in the ER (endoplasmic reticulum). However, the length of the peptides are strictly restricted in the process of peptide transporting, processing and presentation. A hypothesis is proposed that the abnormal mechanism of AS may related to the trimming of N-terminal sequences from antigenic precursors in the ER and the length of the antigenic peptides that are presented to the T-cell receptors. (C) 2012 Elsevier Ltd. All rights reserved.