5DD5

Crystal structures in an anti-HIV antibody lineage from immunization of Rhesus macaques

Summary for 5DD5

• Entry DOI: 10.2210/pdb5dd5/pdb
• Related: 5DD0 5DD1 5DD3 5DD6 5DQD 5DQJ
• Descriptor: ANTI-HIV ANTIBODY DH570.9 FAB HEAVY CHAIN (3 entities in total)
• Functional Keywords: hiv hiv-1 gp41 mper antibody, immune system
• Biological source: Macaca mulatta; More
• Total number of polymer chains: 2
• Total formula weight: 48042.40

Authors

Nicely, N.I.,Pemble IV, C.W.,Haynes, B.F. (deposition date: 2015-08-24, release date: 2016-05-11, Last modification date: 2023-09-27)

Primary citation

Zhang, R.,Verkoczy, L.,Wiehe, K.,Munir Alam, S.,Nicely, N.I.,Santra, S.,Bradley, T.,Pemble, C.W.,Zhang, J.,Gao, F.,Montefiori, D.C.,Bouton-Verville, H.,Kelsoe, G.,Larimore, K.,Greenberg, P.D.,Parks, R.,Foulger, A.,Peel, J.N.,Luo, K.,Lu, X.,Trama, A.M.,Vandergrift, N.,Tomaras, G.D.,Kepler, T.B.,Moody, M.A.,Liao, H.X.,Haynes, B.F.
Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages.
Sci Transl Med, 8:336ra62-336ra62, 2016

PubMed Abstract: Development of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used gp41 2F5 bnAb germline knock-in mice and macaques vaccinated with immunogens reactive with germline precursors to activate neutralizing antibodies. In germline knock-in mice, bnAb precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M (IgM). Immunized macaques made B cell clonal lineages targeted to the 2F5 bnAb epitope, but 2F5-like antibodies were either deleted or did not attain sufficient affinity for gp41-lipid complexes to achieve the neutralization potency of 2F5. Structural analysis of members of a vaccine-induced antibody lineage revealed that heavy chain complementarity-determining region 3 (HCDR3) hydrophobicity was important for neutralization. Thus, gp41 bnAbs are controlled by immune tolerance, requiring vaccination strategies to transiently circumvent tolerance controls.

PubMed: 27122615
DOI: 10.1126/scitranslmed.aaf0618

Experimental method

X-RAY DIFFRACTION (1.9 Å)