From structure to sequence: Antibody discovery using cryoEM-Reference-Cited by-同舟云学术

From structure to sequence: Antibody discovery using cryoEM

Published:2022-01-21 Issue:3 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Antanasijevic Aleksandar¹²^ORCID,Bowman Charles A.¹²^ORCID,Kirchdoerfer Robert N.³^ORCID,Cottrell Christopher A.²⁴^ORCID,Ozorowski Gabriel¹²^ORCID,Upadhyay Amit A.⁵⁶^ORCID,Cirelli Kimberly M.⁷,Carnathan Diane G.⁶,Enemuo Chiamaka A.⁶,Sewall Leigh M.¹,Nogal Bartek¹^ORCID,Zhao Fangzhu⁴⁸^ORCID,Groschel Bettina²⁴^ORCID,Schief William R.²⁴⁹^ORCID,Sok Devin²⁴⁸^ORCID,Silvestri Guido⁶^ORCID,Crotty Shane⁷^ORCID,Bosinger Steven E.⁵⁶^ORCID,Ward Andrew B.¹²^ORCID

Affiliation:

1. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

2. Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.

3. Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI 53706, USA.

4. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

5. Department of Pathology and Laboratory Medicine, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA.

6. Yerkes Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Yerkes Nonhuman Primate Genomics Core, Emory University, Atlanta, GA 30329, USA.

7. Vaccine Discovery Division, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

8. International AIDS Vaccine Initiative–Neutralizing Antibody Center (IAVI-NAC), The Scripps Research Institute, La Jolla, CA 92037, USA.

9. The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.

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 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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