The Journal of experimental medicine · 2022
Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lorin Valérie, Fernández Ignacio, Masse-Ranson Guillemette, Bouvin-Pley Mélanie, Molinos-Albert Luis M, Planchais Cyril, Hieu Thierry, Péhau-Arnaudet Gérard, 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 François, Di Santo James P, Rey Félix A, Mouquet Hugo
Аннотация
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-Å 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.