de la Paz P, Sutton B J, Darsley M J, Rees A R
EMBO J. 1986 Feb;5(2):415-25. doi: 10.1002/j.1460-2075.1986.tb04227.x.
Models of the antigen combining sites of three monoclonal antibodies, which recognise different but overlapping epitopes within the 'loop' region of hen egg lysozyme (HEL), have been generated from the cDNA sequences of their Fv regions (the VL and VH domains) and the known crystal structures of immunoglobulin fragments. The alpha-carbon backbone of the structurally conserved framework region has been derived from the IgG myeloma protein NEW, and models for the hypervariable loop regions have been selected on the basis of length and maximum sequence homology. The model structures have been refined by energy minimisation. Both the size and chemical nature of the predicted combining site models correlate broadly with the epitope boundaries previously determined by affinity studies. A model of the complex formed between one antibody and the corresponding lysozyme epitope is described, and contact residues are identified for subsequent testing by oligonucleotide-directed site-specific mutagenesis.
已根据三种单克隆抗体Fv区（VL和VH结构域）的cDNA序列以及免疫球蛋白片段的已知晶体结构，构建了这三种单克隆抗体抗原结合位点的模型。这三种单克隆抗体识别鸡卵溶菌酶（HEL）“环”区域内不同但重叠的表位。结构保守框架区的α-碳主链取自IgG骨髓瘤蛋白NEW，并根据长度和最大序列同源性选择了高变环区域的模型。通过能量最小化对模型结构进行了优化。预测的结合位点模型的大小和化学性质与先前通过亲和力研究确定的表位边界大致相关。描述了一种抗体与相应溶菌酶表位形成的复合物模型，并鉴定了接触残基，以便随后通过寡核苷酸定向位点特异性诱变进行测试。
