5F6H

Crystal Structure of Tier 2 Neutralizing Antibody DH427 from a Rhesus Macaque

Summary for 5F6H

• Entry DOI: 10.2210/pdb5f6h/pdb
• Related: 5F6I 5F6J
• Descriptor: DH427 Antibody Light Chain, DH427 Antibody Heavy Chain (3 entities in total)
• Functional Keywords: fab fragment, hiv-1, antibody, immune system
• Biological source: Macaca mulatta; More
• Total number of polymer chains: 8
• Total formula weight: 188416.97

Authors

Fera, D.,Harrison, S.C. (deposition date: 2015-12-06, release date: 2016-01-13, Last modification date: 2024-10-23)

Primary citation

Bradley, T.,Fera, D.,Bhiman, J.,Eslamizar, L.,Lu, X.,Anasti, K.,Zhang, R.,Sutherland, L.L.,Scearce, R.M.,Bowman, C.M.,Stolarchuk, C.,Lloyd, K.E.,Parks, R.,Eaton, A.,Foulger, A.,Nie, X.,Karim, S.S.,Barnett, S.,Kelsoe, G.,Kepler, T.B.,Alam, S.M.,Montefiori, D.C.,Moody, M.A.,Liao, H.X.,Morris, L.,Santra, S.,Harrison, S.C.,Haynes, B.F.
Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.
Cell Rep, 14:43-54, 2016

PubMed Abstract: Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.

PubMed: 26725118
DOI: 10.1016/j.celrep.2015.12.017

Experimental method

X-RAY DIFFRACTION (2.66 Å)