LOCALIZATION OF THE BINDING-SITE FOR THE HUMAN HIGH-AFFINITY FC RECEPTOR ON IGG
LOCALIZATION OF THE BINDING-SITE FOR THE HUMAN HIGH-AFFINITY FC RECEPTOR ON IGG
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DOI：
10.1038/332563a0
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发表时间：
1988-04-07
期刊：
影响因子：
64.8
通讯作者：
WINTER, G
中科院分区：
文献类型：
--
作者：
DUNCAN, AR;WOOF, JM;WINTER, G
病原体清除的主要途径涉及用特异性抗体包被病原体，以及抗体Fc区与细胞受体的结合。这可以触发吞噬细胞对病原体的吞噬或杀伤细胞的溶解。通过寡核苷酸定点突变，我们在小鼠IgG2b抗体中设计了一个单一的氨基酸变化（Glu 235 → Leu），这现在使该抗体能够与人单核细胞上的FcRI（高亲和力）受体结合，亲和力提高了100倍。这表明Leu 235是抗体与FcRI结合的主要决定因素，并且受体可以与连接CH2结构域与铰链的区域直接相互作用。调整抗体对细胞受体的亲和力有助于剖析它们在清除病原体中的作用。
A major pathway in the clearance of pathogens involves the coating of the pathogen with specific antibodies, and the binding of the antibody Fc region to cell receptors. This can trigger engulfment of the pathogen by phagocytes or lysis by killer cells. By oligo-nucleotide site-directed mutagenesis we have engineered a single amino acid change in a mouse IgG2b antibody (Glu 235 → Leu) which now enables the antibody to bind to the FcRI (high affinity) receptor on human monocytes with a 100-fold improvement in affinity. This indicates that Leu 235 is a major determinant in the binding of antibody to FcRI and that the receptor may interact directly with the region linking the CH2 domain to the hinge. Tailoring the affinity of antibodies for cell receptors could help dissect their role in clearing pathogen.