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From structure to sequence: Antibody discovery using cryoEM
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DOI：10.1126/sciadv.abk2039.png)
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Abstract
En 中文
One of the rate-limiting steps in analyzing immune responses to vaccines or infections is the isolation and characterization of monoclonal antibodies. Here, we present a hybrid structural and bioinformatic approach to directly assign the heavy and light chains, identify complementarity-determining regions, and discover sequences from cryoEM density maps of serum-derived polyclonal antibodies bound to an antigen. When combined with next-generation sequencing of immune repertoires, we were able to specifically identify clonal family members, synthesize the monoclonal antibodies, and confirm that they interact with the antigen in a manner equivalent to the corresponding polyclonal antibodies. This structure-based approach for identification of monoclonal antibodies from polyclonal sera opens new avenues for analysis of immune responses and iterative vaccine design.
Keywords:
MONOCLONAL-ANTIBODIES
NONHUMAN-PRIMATES
HIV
RESPONSES
IDENTIFICATION
IMMUNOGLOBULIN
VISUALIZATION
TECHNOLOGIES
GENERATION
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