5UKO

Structure of unliganded anti-gp120 CD4bs antibody DH522IA Fab

5UKO の概要

• エントリーDOI: 10.2210/pdb5uko/pdb
• 関連するPDBエントリー: 5UKN 5UKP 5UKQ 5UKR
• 分子名称: DH522IA Fab fragment heavy chain, DH522IA Fab fragment light chain (3 entities in total)
• 機能のキーワード: hiv gp120 immune system, immune system
• 由来する生物種: Macaca mulatta; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47273.42

構造登録者

Nicely, N.I. (登録日: 2017-01-23, 公開日: 2017-12-06, 最終更新日: 2023-10-04)

主引用文献

Williams, W.B.,Zhang, J.,Jiang, C.,Nicely, N.I.,Fera, D.,Luo, K.,Moody, M.A.,Liao, H.X.,Alam, S.M.,Kepler, T.B.,Ramesh, A.,Wiehe, K.,Holland, J.A.,Bradley, T.,Vandergrift, N.,Saunders, K.O.,Parks, R.,Foulger, A.,Xia, S.M.,Bonsignori, M.,Montefiori, D.C.,Louder, M.,Eaton, A.,Santra, S.,Scearce, R.,Sutherland, L.,Newman, A.,Bouton-Verville, H.,Bowman, C.,Bomze, H.,Gao, F.,Marshall, D.J.,Whitesides, J.F.,Nie, X.,Kelsoe, G.,Reed, S.G.,Fox, C.B.,Clary, K.,Koutsoukos, M.,Franco, D.,Mascola, J.R.,Harrison, S.C.,Haynes, B.F.,Verkoczy, L.
Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.
Nat Commun, 8:1732-1732, 2017

PubMed Abstract: A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice EnvB cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env upon receptor editing. In comparison with repetitive Env immunizations, sequential Env administration rescue anergic Env (non-edited) precursor B cells. Thus, stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development, suggesting that sequential immunogen-based vaccine regimens will likely need to incorporate strategies to expand bnAb precursor pools.

PubMed: 29170366
DOI: 10.1038/s41467-017-01336-3

実験手法

X-RAY DIFFRACTION (2.3 Å)