Autoimmune epitopes: autoepitopes
Autoimmune epitopes: autoepitopes
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DOI：
10.1016/j.autrev.2004.07.011
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发表时间：
2004-11-01
影响因子：
13.6
通讯作者：
Rowley, MJ
中科院分区：
文献类型：
--
作者：
Mackay, IR;Rowley, MJ
自身抗体反应物的身份已从整个细胞器（免疫荧光）、识别的分子（免疫印迹；基因表达文库）、表位区域（截短的 cDNA；肽扫描）到接触残基相继完善，如此处所述。大多数自身抗体与构象表位发生反应，其中线性序列中距离较远的氨基酸通过蛋白质折叠而变得邻近。鉴定与抗体互补位的接触位点需要特殊的技术、晶体学或噬菌体展示的随机肽库的自身筛选。我们对原发性胆汁性肝硬化 (PBC) 中抗 PDC-E2 (AMA) 自身表位、1 型糖尿病中抗 GAD65 以及胶原诱导性关节炎中 II 型胶原抗 C1 自身表位的研究说明了后者。构象自身表位结构的更精确定义可以（a）澄清自身免疫的有争议的方面，包括表位模拟、表位扩散以及 B 和 T 细胞自身表位之间的分子空间关系，以及（b）对新型诊断和治疗（疫苗）分子的影响。 (C) 2004 年由 Elsevier B.V. 出版
The identity of reactants for autoantibodies has been successively refined from whole cellular organelles (immunofluorescence), identified molecules (immunoblot; gene expression libraries), epitope regions (truncated cDNAs; peptide scanning) to contact residues, as described here. Most autoantibodies react with conformational epitopes, in which amino acids distant in the linear sequence come into contiguity by protein folding. Identification of contact sites with the antibody paratope requires particular technologies, crystallography, or autobody screening of phage-displayed random peptide libraries. The latter is illustrated by our studies on the autoepitope for anti-PDC-E2 (AMA) in primary biliary cirrhosis (PBC), anti-GAD65 in type 1 diabetes and anti-C1 of type II collagen in collagen-induced arthritis. More precise definition of the structure of conformational autoepitopes could (a) clarify controversial aspects of autoimmunity including epitope mimicry, epitope spreading, and molecular spatial relationships between B and T cell autoepitopes, and (b) impact on novel diagnostic and therapeutic (vaccine) molecules. (C) 2004 Published by Elsevier B.V.