From structure to sequence: Antibody discovery using cryoEM

被引：28

作者：

Antanasijevic, Aleksandar ^{[1
,2
]}

Bowman, Charles A. ^{[1
,2
]}

Kirchdoerfer, Robert N. ^{[3
]}

Cottrell, Christopher A. ^{[2
,4
]}

Ozorowski, Gabriel ^{[1
,2
]}

Upadhyay, Amit A. ^{[5
,6
,7
]}

Cirelli, Kimberly M. ^{[8
]}

Carnathan, Diane G. ^{[6
,7
]}

Enemuo, Chiamaka A. ^{[6
,7
]}

Sewall, Leigh M. ^{[1
]}

Nogal, Bartek ^{[1
]}

Zhao, Fangzhu ^{[4
,9
]}

Groschel, Bettina ^{[2
,4
]}

Schief, William R. ^{[2
,4
,10
,11
]}

Sok, Devin ^{[2
,4
,9
]}

Silvestri, Guido ^{[6
,7
]}

Crotty, Shane ^{[8
]}

Bosinger, Steven E. ^{[5
,6
,7
]}

Ward, Andrew B. ^{[1
,2
]}

机构：

[1] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Consortium HIV AIDS Vaccine Dev CHAVD, La Jolla, CA 92037 USA

[3] Univ Wisconsin, Coll Agr & Life Sci, Dept Biochem, Madison, WI 53706 USA

[4] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA

[5] Emory Univ, Emory Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30329 USA

[6] Emory Univ, Yerkes Natl Primate Res Ctr, Yerkes Div Microbiol & Immunol, Atlanta, GA 30329 USA

[7] Emory Univ, Yerkes Nonhuman Primate Genom Core, Atlanta, GA 30329 USA

[8] La Jolla Inst Immunol, Vaccine Discovery Div, La Jolla, CA 92037 USA

[9] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA

[10] MIT, Ragon Inst, Massachusetts Gen Hosp, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[11] Harvard Univ, Cambridge, MA 02139 USA

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 03期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

MONOCLONAL-ANTIBODIES; NONHUMAN-PRIMATES; HIV; RESPONSES; IDENTIFICATION; IMMUNOGLOBULIN; VISUALIZATION; TECHNOLOGIES; GENERATION;

D O I：

10.1126/sciadv.abk2039

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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