Integrative proteomics identifies thousands of distinct, multi-epitope, and high-affinity nanobodies.

ABSTRACT: The antibody immune response is essential for the survival of mammals. However, we still lack a systematic understanding of the antibody repertoire. Here, we developed a proteomic strategy to survey, at an unprecedented scale, the landscape of antigen-engaged, circulating camelid heavy-chain antibodies, whose minimal binding fragments are called V_HH antibodies or nanobodies. The sensitivity and robustness of this approach were validated with three antigens spanning orders of magnitude in immune responses; thousands of distinct, high-affinity nanobody families were reliably identified and quantified. Using high-throughput structural modeling, cross-linking mass spectrometry, mutagenesis, and deep learning, we mapped and analyzed the epitopes of >100,000 antigen-nanobody complexes

SUBMITTER: Xiang Y 

PROVIDER: S-EPMC7979497 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature