Mutational Analysis of 48G7 Reveals that Somatic Hypermutation Affects Both Antibody Stability and Binding Affinity (Retracted article. See vol. 140, pg. 1976, 2018)
Mutational Analysis of 48G7 Reveals that Somatic Hypermutation Affects Both Antibody Stability and Binding Affinity (Retracted article. See vol. 140, pg. 1976, 2018)
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DOI：
10.1021/ja402927u
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发表时间：
2013-07-10
影响因子：
15
通讯作者：
Wang, Feng
中科院分区：
文献类型：
--
作者：
Sun, Sophie B.;Sen, Shiladitya;Wang, Feng
单抗48G7与其生殖系前体有10个体细胞突变，其中一些似乎在功能上是沉默的。我们分析了单个体细胞突变及其组合对抗体结合亲和力和热稳定性的影响。增强与半抗原结合亲和力的单个体细胞突变会降低种系抗体的稳定性；将这些结合突变组合在一起会产生一个对半抗原具有高亲和力但稳定性极低的突变体。把剩下的每一个体细胞突变都加回去，恢复了热稳定性。这些结果，结合最近发表的研究，表明了体细胞超突变的作用扩大，在克隆选择过程中，结合亲和力和稳定性都得到了优化。
The monoclonal antibody 48G7 differs from its germline precursor by 10 somatic mutations, a number of which appear to be functionally silent. We analyzed the effects of individual somatic mutations and combinations thereof on both antibody binding affinity and thermal stability. Individual somatic mutations that enhance binding affinity to hapten decrease the stability of the germline antibody; combining these binding mutations produced a mutant with high affinity for hapten but exceptionally low stability. Adding back each of the remaining somatic mutations restored thermal stability. These results, in conjunction with recently published studies, suggest an expanded role for somatic hypermutation in which both binding affinity and stability are optimized during clonal selection.