在肽库中筛选抗磷脂抗体的小肽抑制剂

β２糖蛋白Ⅰ（ｂｅｔａ－２－ｇｌｙｃｏｐｒｏｔｅｉｎ Ⅰ，β２ＧＰＩ）是一分子量为５０ ｋＤ的糖蛋白．从抗磷脂抗体综合症（Ａｎｔｉｐｈｏｓｐｈｏｌｉｐｉｄ ａｎｔｉｂｏｄｉｅｓ ｓｙｎｄｒｏｍ ，ＡＰＳ）患者身上获得的抗体可直接与β２ＧＰＩ作用．以β２ＧＰＩ为目标分子，在噬菌体十五肽库中筛选抗β２糖蛋白Ⅰ抗体的小肽抑制剂．通过四轮亲和性筛选，噬菌体的回收率从１．２６×１０－ ４％ 增加到３．１９×１０－ ２％ ．随机挑取噬菌体克隆测定其与β２ＧＰＩ的结合活性及其对β２ＧＰＩ与自身抗体结合的抑制活性，其中部分噬菌体克隆表现出４０％ 的抑制活性．经ＤＮＡ 序列测定，得到一组相关序列．该结果为研究β２ＧＰＩ的抗原表位奠定了良好的基础．

Antiphospholipid Antibodies Inhibitors Screened by Using Phage Display Peptide Library

Glycoprotein Ⅰ(β 2GPI) has been identified as a cofactor in recognition of the antiphospholipid antibodies. β 2GPI was used as a probe to screen affinity phage clones panning from a phage peptide library. After four consecutive panning rounds, the phage recovery increased from 1.26×10 -4 % to 3.19×10 -2 %. It means that specific enrichment had been achieved. In order to characterize these phage clones, their specific binding to β 2GPI and their inhibition of β 2GPI binding to antiphospholipid antibodies were investigated.Among them, the motif( FSL V SS ) for binding β 2GPI was identified by DNA sequencing.The selected phage peptides identically specific for the same epitopes might specifically block the anti β 2GPI antibodies binding to β 2GPI. Indeed the motif ( FSL ) was important for the phage peptides binding to β 2GPI. The results also supported the idea that anti β 2GPI antibodies occurred in the sera of patients with autoimmune diseases.