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-Structure paper
タイトル | Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller. |
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ジャーナル・号・ページ | J Exp Med, Vol. 219, Issue 3, Year 2022 |
掲載日 | 2022年3月7日 |
著者 | Valérie 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 要旨 | 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 ...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. |
リンク | J Exp Med / PubMed:35230385 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.8 - 7.0 Å |
構造データ | EMDB-13316, PDB-7pc2: EMDB-13332: EMDB-13333: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / HIV / antibody / bNAb / Env |