Informace o publikaci

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

Autoři	LORIN Valerie FERNANDEZ Ignacio MASSE-RANSON Guillemette BOUVIN-PLEY Melanie MOLINOS-ALBERT Luis M PLANCHAIS Cyril HIEU Thierry PEHAU-ARNAUDET Gerard HREBÍK Dominik GIRELLI-ZUBANI Giulia FIQUET Oriane GUIVEL-BENHASSINE Florence SANDERS Rogier W WALKER Bruce D SCHWARTZ Olivier SCHEID Johannes F DIMITROV Jordan D PLEVKA Pavel BRAIBANT Martine SEAMAN Michael S BONTEMS Francois DI SANTO James p REY Felix A MOUQUET Hugo
Rok publikování	2022
Druh	Článek v odborném periodiku
Časopis / Zdroj	JOURNAL OF EXPERIMENTAL MEDICINE
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	https://rupress.org/jem/article/219/3/e20212045/213042/Epitope-convergence-of-broadly-HIV-1-neutralizing
Doi	http://dx.doi.org/10.1084/jem.20212045
Klíčová slova	B-CELLSSTANDARDIZED ASSESSMENTSENVELOPE GLYCOPROTEINEFFICIENT GENERATIONMONOCLONAL-ANTIBODYCRYSTAL-STRUCTUREPOTENTGLYCANGP120MATURATION
Popis	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.