Keen Meredith M, Keith Alasdair D, Ortlund Eric A
Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, Georgia, USA.
Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, Georgia, USA.
J Biol Chem. 2025 Jan;301(1):108072. doi: 10.1016/j.jbc.2024.108072. Epub 2024 Dec 14.
Epitope mapping is a technique employed to define the region of an antigen that elicits an immune response, providing crucial insight into the structural architecture of the antigen as well as epitope-paratope interactions. With this breadth of knowledge, immunotherapies, diagnostics, and vaccines are being developed with a rational and data-supported design. Traditional epitope mapping methods are laborious, time-intensive, and often lack the ability to screen proteins in a high-throughput manner or provide high resolution. Deep mutational scanning (DMS), however, is revolutionizing the field as it can screen all possible single amino acid mutations and provide an efficient and high-throughput way to infer the structures of both linear and three-dimensional epitopes with high resolution. Currently, more than 50 publications take this approach to efficiently identify enhancing or escaping mutations, with many then employing this information to rapidly develop broadly neutralizing antibodies, T-cell immunotherapies, vaccine platforms, or diagnostics. We provide a comprehensive review of the approaches to accomplish epitope mapping while also providing a summation of the development of DMS technology and its impactful applications.
表位作图是一种用于确定引发免疫反应的抗原区域的技术，它能为抗原的结构架构以及表位-互补位相互作用提供关键见解。基于这些广泛的知识，正在以合理且有数据支持的设计来开发免疫疗法、诊断方法和疫苗。传统的表位作图方法既费力又耗时，而且往往缺乏以高通量方式筛选蛋白质或提供高分辨率的能力。然而，深度突变扫描（DMS）正在彻底改变这一领域，因为它可以筛选所有可能的单氨基酸突变，并提供一种高效且高通量的方法来高分辨率推断线性和三维表位的结构。目前，有50多篇出版物采用这种方法来有效识别增强或逃逸突变，许多研究随后利用这些信息迅速开发广泛中和抗体、T细胞免疫疗法、疫苗平台或诊断方法。我们对完成表位作图的方法进行了全面综述，同时也总结了DMS技术的发展及其有影响力的应用。
