6XOC

Crystal structure of glVRC01 Fab in complex with anti-idiotypic iv4 Fab

6XOC の概要

• エントリーDOI: 10.2210/pdb6xoc/pdb
• 分子名称: Iv4 Fab Heavy Chain, IV4 Fab Light Chain, iGL-VRC01 Fab Heavy Chain, ... (10 entities in total)
• 機能のキーワード: fab, complex, immune system, hiv, cd4-binding site
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95627.74

構造登録者

Aljedani, S.S.,Weidle, C.,Pancera, M. (登録日: 2020-07-06, 公開日: 2021-03-31, 最終更新日: 2023-10-18)

主引用文献

Seydoux, E.,Wan, Y.H.,Feng, J.,Wall, A.,Aljedani, S.,Homad, L.J.,MacCamy, A.J.,Weidle, C.,Gray, M.D.,Brumage, L.,Taylor, J.J.,Pancera, M.,Stamatatos, L.,McGuire, A.T.
Development of a VRC01-class germline targeting immunogen derived from anti-idiotypic antibodies.
Cell Rep, 35:109084-109084, 2021

PubMed Abstract: An effective HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs). Broad and potent VRC01-class bNAbs have been isolated from multiple infected individuals, suggesting that they could be reproducibly elicited by vaccination. Several HIV-1 envelope-derived germline-targeting immunogens have been designed to engage naive VRC01-class precursor B cells. However, they also present off-target epitopes that could hinder development of VRC01-class bNAbs. We characterize a panel of anti-idiotypic monoclonal antibodies (ai-mAbs) raised against inferred-germline (iGL) VRC01-class antibodies. By leveraging binding, structural, and B cell sorting data, we engineered a bispecific molecule derived from two ai-mAbs; one specific for VRC01-class heavy chains and one specific for VRC01-class light chains. The bispecific molecule preferentially activates iGL-VRC01 B cells in vitro and induces specific antibody responses in a murine adoptive transfer model with a diverse polyclonal B cell repertoire. This molecule represents an alternative non-envelope-derived germline-targeting immunogen that can selectively activate VRC01-class precursors in vivo.

PubMed: 33951425
DOI: 10.1016/j.celrep.2021.109084

実験手法

X-RAY DIFFRACTION (2.45 Å)