对48G7的突变分析表明,体变异会影响抗体的稳定性和结合亲和力
Sophie B Sun1, Shiladitya Sen, Nam-Jung Kim
1Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|June 26, 2013
概括
抗体中的体质突变可以增强结合亲和力,但降低稳定性. 进一步的突变可以恢复稳定性,这表明体质突变优化了免疫反应期间的抗体结合和稳定性.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 抗体经历体质突变,以改善抗原结合.
- 人体突变对抗体稳定性的影响不太清楚.
- 单克隆抗体48G7为研究这些效应提供了一个模型.
研究的目的:
- 研究个人和组合体质突变对抗体结合亲和力和热稳定性的影响.
- 阐明体质突变在优化抗体功能的作用.
主要方法:
- 对48G7抗体中个体体质突变的分析.
- 测定绑定 afinity 对 hapten 的评价.
- 测量抗体变体的热稳定性.
主要成果:
- 个别突变增强结合亲和力降低了抗体稳定性.
- 产生了一个具有高亲和力和低稳定性的突变物.
- 额外的体质突变恢复了抗体的热稳定性.
结论:
- 身体突变具有双重作用,影响抗体亲和力和稳定性.
- 身体突变可能在克隆选择过程中优化结合亲和力和稳定性.
- 这些发现扩大了对抗体进化和免疫反应的理解.
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