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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F22%3A00127891" target="_blank" >RIV/00216224:14740/22:00127891 - isvavai.cz</a>

Výsledek na webu

<a href="https://rupress.org/jem/article/219/3/e20212045/213042/Epitope-convergence-of-broadly-HIV-1-neutralizing" target="_blank" >https://rupress.org/jem/article/219/3/e20212045/213042/Epitope-convergence-of-broadly-HIV-1-neutralizing</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1084/jem.20212045" target="_blank" >10.1084/jem.20212045</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

JOURNAL OF EXPERIMENTAL MEDICINE

ISSN

0022-1007

e-ISSN

—

Svazek periodika

219

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

21

Strana od-do

1-21

Kód UT WoS článku

000867703500001

EID výsledku v databázi Scopus

2-s2.0-85126474984