Big data and structural proteomics allow epitope mapping of over 100,000 antigen-nanobody complexes.


The humoral antibody immune response is universal and critical for the survival of mammals, including humans. However, there is a lack of understanding of the antibody immune response mechanisms. Studying antigen-nanobody (Nb) interactions provides insights into the mammalian humoral immunity and the underlying disease mechanisms.

Despite enormous efforts in characterizing antigen-antibody interactions and structural characterization of specific binary interactions, the circulating antibody repertoire that responds to an antigen is not well understood. In this study, Xiang et al developed a new integrative proteomics strategy that enables global identification, classification, and high-throughput structural characterization of antigen-specific Nbs.

The group developed a multidisciplinary approach using structural modeling, cross-linking mass spectrometry, mutagenesis and machine learning. Relying on the latest IonOpticks Aurora Series columns for liquid chromatography-mass spectrometry, they were able to map and analyze the epitopes of over 100,000 antigen-Nb complexes.

The developed proteomic workflow enabled survey of the landscape of antigen-engaged heavy chain camelid antibodies, and by coupling with high-throughput structural modelling and cross-linking MS, they were able to map thousands of antigen-nanobody complexes and analyze them efficiently. This strategy has revealed the efficiency, specificity, diversity, and versatility of the mammalian humoral immunity. In the future this multidisciplinary platform may drive high-quality Nb discovery and characterization.

Read the full paper
Integrative proteomics identifies thousands of distinct, multi-epitope, and high-affinity nanobodies.
Cell Systems. 2021 Mar 17;12(3):220-234.e9. doi: https://doi.org/10.1016/j.cels.2021.01.003
Yufei Xiang, Zhe Sang, Lirane Bitton, Jianquan Xu, Yang Liu, Dina Schneidman-Duhovny, Yi Shi

Commentary by Amr S Abbadi, PhD candidate.

About the author
Amr is a PhD candidate in comparative biomedical sciences at the University of Georgia, USA. He has also worked as a freelance writer and digital marketer for five years. Amr received his MSc in Pharmaceutical Biotechnology from the University of Padova in Italy, and graduated from the Suez Canal University in Egypt with a BSc in Clinical Pharmacy.