Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller

被引：17

作者：

Lorin, Valerie ^{[1
,2
,3
]}

Fernandez, Ignacio ^{[4
,5
]}

Masse-Ranson, Guillemette ^{[6
,7
]}

Bouvin-Pley, Melanie ^{[8
]}

Molinos-Albert, Luis M. ^{[1
,2
]}

Planchais, Cyril ^{[1
,2
]}

Hieu, Thierry ^{[1
,2
]}

Pehau-Arnaudet, Gerard ^{[9
,10
]}

Hrebik, Dominik ^{[11
]}

Girelli-Zubani, Giulia ^{[6
,7
]}

Fiquet, Oriane ^{[6
,7
]}

Guivel-Benhassine, Florence ^{[5
,12
]}

Sanders, Rogier W. ^{[13
,14
]}

Walker, Bruce D. ^{[15
,16
,17
,18
]}

Schwartz, Olivier ^{[5
,12
]}

Scheid, Johannes F. ^{[19
]}

Dimitrov, Jordan D. ^{[20
]}

Plevka, Pavel ^{[11
]}

Braibant, Martine ^{[8
]}

Seaman, Michael S. ^{[21
]}

Bontems, Francois ^{[4
,22
]}

Di Santo, James P. ^{[6
,7
]}

Rey, Felix A. ^{[4
,5
]}

Mouquet, Hugo ^{[1
,2
]}

机构：

[1] Inst Pasteur, Dept Immunol, Lab Humoral Immunol, Paris, France

[2] INSERM, U1222, Paris, France

[3] Univ Paris, Sorbonne Paris Cite, Paris, France

[4] Inst Pasteur, Dept Virol, Struct Virol Unit, Paris, France

[5] CNRS, URA3015, Paris, France

[6] Inst Pasteur, Dept Immunol, Innate Immun Unit, Paris, France

[7] INSERM, U1223, Paris, France

[8] Univ Tours, INSERM, U1259, Tours, France

[9] Inst Pasteur, Plate Forme Microscopie Ultrastruct, Imagopole, Paris, France

[10] Inst Pasteur, UMR 3528, Paris, France

[11] Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic

[12] Inst Pasteur, Dept Virol, Virus & Immun Unit, Paris, France

[13] Univ Amsterdam, Med Ctr, Amsterdam Infect & Immun Inst, Dept Med Microbiol,Amsterdam Univ, Amsterdam, Netherlands

[14] Cornell Univ, Dept Microbiol & Immunol, Weill Med Coll, New York, NY 10021 USA

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

[16] Harvard, Cambridge, MA USA

[17] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

[18] Harvard Med Sch, Charlestown, MA USA

[19] Rockefeller Univ, Lab Mol Immunol, 1230 York Ave, New York, NY 10021 USA

[20] Sorbonne Univ, Univ Paris, Ctr Rech Cordeliers, INSERM, Paris, France

[21] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[22] Univ Paris Saclay, CNRS, Inst Chim Subst Nat, Gif Sur Yvette, France

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2022年 / 219卷 / 03期

基金：

欧洲研究理事会;

关键词：

B-CELLS; STANDARDIZED ASSESSMENTS; ENVELOPE GLYCOPROTEIN; EFFICIENT GENERATION; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; POTENT; GLYCAN; GP120; MATURATION;

D O I：

10.1084/jem.20212045

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies (bNAbs) is paramount for vaccine design. Here, we characterized IgA and IgG bNAbs of three distinct B cell lineages in a viremic controller, two of which comprised only IgG(+) or IgA(+) blood memory B cells; the third combined both IgG and IgA clonal variants. 7-269 bNAb in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation, and delayed viral rebound in humanized mice. bNAbs in all three lineages targeted the N332 glycan supersite. The 2.8-angstrom resolution cryo-EM structure of 7-269-BG505 SOSIP.664 complex showed a similar pose as 2G12, on an epitope mainly composed of sugar residues comprising the N332 and N295 glycans. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers.

引用

页数：27

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