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TitleEpitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller.
Journal, issue, pagesJ Exp Med, Vol. 219, Issue 3, Year 2022
Publish dateMar 7, 2022
AuthorsValérie Lorin / Ignacio Fernández / Guillemette Masse-Ranson / Mélanie Bouvin-Pley / Luis M Molinos-Albert / Cyril Planchais / Thierry Hieu / Gérard Péhau-Arnaudet / Dominik Hrebík / Giulia Girelli-Zubani / Oriane Fiquet / Florence Guivel-Benhassine / Rogier W Sanders / Bruce D Walker / Olivier Schwartz / Johannes F Scheid / Jordan D Dimitrov / Pavel Plevka / Martine Braibant / Michael S Seaman / François Bontems / James P Di Santo / Félix A Rey / Hugo Mouquet /
PubMed AbstractDecrypting 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 ...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.
External linksJ Exp Med / PubMed:35230385 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 7.0 Å
Structure data

13316

7pc2

EMDB-13316, PDB-7pc2:
HIV-1 Env (BG505 SOSIP.664) in complex with the IgA bNAb 7-269 and the antibody 3BNC117.
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-13332:
HIV-1 Env (BG505 SOSIP.664) in complex with the bNAb 7-176
Method: EM (single particle) / Resolution: 7.0 Å

EMDB-13333:
HIV-1 Env (BG505 SOSIP.664) in complex with the bNAb 7-155
Method: EM (single particle) / Resolution: 6.7 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
  • human immunodeficiency virus
KeywordsVIRAL PROTEIN / HIV / antibody / bNAb / Env

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