人类天然抗α-Gal抗体抑制肽的筛选

Screening of Inhibitory Peptides of Human Natural Antibodies From Phage Displayed Library

人类天然抗体可以与猪细胞抗原表位Gal α1,3 Gal结合 ,触发超急性排斥反应 (HAR) ,HAR是猪器官移植至人体时的首要障碍 .阻断人的天然抗体 ,阻止其与猪细胞表面特异性抗原的结合 ,是防止超急性排斥的有效措施 .利用噬菌体展示技术 ,从XCX15随机肽库中筛选与西非单叶豆凝集素 (GS I B4)特异性结合的噬菌体展示肽 .得到一个小肽序列为SCTALSFPSFAFLARGT ,其与人血清中天然抗体的结合可以被蜜二糖(melibiose)竞争性地抑制 ,同时该小肽还能抑制人类天然抗体介导的猪红细胞的凝集反应 .因此 ,筛选到的小肽能作为人天然抗α

The initial barrier to the transplantation of pig organs to human is hyperacute rejection (HAR). HAR was initiated by the conjugation of human natural antibodies (XNA) with the Gal-alpha1,3-Gal which is thought to be the major xenoantigenic epitope present on pig tissues. Removal of antibodies directly against that structure may be critical to the success of pig to human xenotransplantation. The lectin GS-I-B-4 was used to screen phage-displayed peptide library XCX15 and identified a peptide mimetic of Gal-alpha1,3-Gal. A phage bearing the peptide SCTALSFPSFAFLARGT has been identified to bind human natural antibody strongly. This binding reaction can be competitively inhibited by melibiose. The peptide can also inhibit the human natural antibody-mediated agglutination of pig RBCs.