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-Structure paper
Title | From structure to sequence: Antibody discovery using cryoEM. |
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Journal, issue, pages | Sci Adv, Vol. 8, Issue 3, Page eabk2039, Year 2022 |
Publish date | Jan 21, 2022 |
Authors | Aleksandar Antanasijevic / Charles A Bowman / Robert N Kirchdoerfer / Christopher A Cottrell / Gabriel Ozorowski / Amit A Upadhyay / Kimberly M Cirelli / Diane G Carnathan / Chiamaka A Enemuo / Leigh M Sewall / Bartek Nogal / Fangzhu Zhao / Bettina Groschel / William R Schief / Devin Sok / Guido Silvestri / Shane Crotty / Steven E Bosinger / Andrew B Ward / |
PubMed Abstract | 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 ...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. |
External links | Sci Adv / PubMed:35044813 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.3 - 15.9 Å |
Structure data | EMDB-23778: EMDB-23779: BG505 SOSIP.v5.2 in complex with the polyclonal Fab pAbC-1 from animal Rh.4O9 EMDB-23780, PDB-7mdu: EMDB-23801, PDB-7mep: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN / monoclonal antibody / polyclonal antibody / immune complex / monoclonal antibodies / HIV-1 / BG505 SOSIP |