ArticleJournal of virology2003
Molecular features of the broadly neutralizing immunoglobulin G1 b12 required for recognition of human immunodeficiency virus type 1 gp120.
Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 104 citations in OpenAlex.
- Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial.PLoS pathogens · 2017Trial
- Preclinical development of mecbotamab vedotin (BA3011), a novel, AXL-specific conditional active biologic antibody-drug conjugate.Antibody therapeutics · 2025Article
- Anti-HIV Humoral Response Induced by Different Anti-Idiotype Antibody Formats: An In Silico and In Vivo Approach.International journal of molecular sciences · 2024Article
- A VRC13-like bNAb response is associated with complex escape pathways in HIV-1 envelope.Journal of virology · 2024Article
- Neutralizing the threat: harnessing broadly neutralizing antibodies against HIV-1 for treatment and prevention.Microbial cell (Graz, Austria) · 2024Article
- Broadly neutralizing antibodies targeting HIV: Progress and challenges.Clinical immunology (Orlando, Fla.) · 2023Review
- IgG1-b12-HIV-gp120 Interface in Solution: A Computational Study.Journal of chemical information and modeling · 2022Article
- Review
- Generating tumor-selective conditionally active biologic anti-CTLA4 antibodies via protein-associated chemical switches.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Signature of Antibody Domain Exchange by Native Mass Spectrometry and Collision-Induced Unfolding.Analytical chemistry · 2018Article
- Structural Analysis of the Glycosylated Intact HIV-1 gp120-b12 Antibody Complex Using Hydroxyl Radical Protein Footprinting.Biochemistry · 2017Article
- Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors.Retrovirology · 2016Article
- Structure-Based Reverse Vaccinology Failed in the Case of HIV Because it Disregarded Accepted Immunological Theory.International journal of molecular sciences · 2016Review
- Monoclonal and Single Domain Antibodies Targeting β-Integrin Subunits Block Sexual Transmission of HIV-1 in In Vitro and In Vivo Model Systems.Journal of acquired immune deficiency syndromes (1999) · 2015Article
- Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01.PloS one · 2015Article
- A novel VHH antibody targeting the B cell-activating factor for B-cell lymphoma.International journal of molecular sciences · 2014Article
- Broadly neutralizing influenza hemagglutinin stem-specific antibody CR8020 targets residues that are prone to escape due to host selection pressure.Cell host & microbe · 2014Article
- The past, present and future of neutralizing antibodies for hepatitis C virus.Antiviral research · 2014Review
- Article
- Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer.Science (New York, N.Y.) · 2013Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
IgG1 b12 is a broadly neutralizing antibody against human immunodeficiency virus type 1 (HIV-1). The epitope recognized by b12 overlaps the CD4 receptor-binding site (CD4bs) on gp120 and has been a target for vaccine design. Determination of the three-dimensional structure of immunoglobulin G1 (IgG1) b12 allowed modeling of the b12-gp120 interaction in which the protruding third complementarity-determining region (CDR) of the heavy chain (H3) was crucial for antibody binding. In the present study, extensive mutational analysis of the antigen-binding site of Fab b12 was carried out to investigate the validity of the model and to identify residues important for gp120 recognition and, by inference, key to the anti-HIV-1 activity of IgG1 b12. In all, 50 mutations were tested: 40 in H3, 4 each in H2 and L1, and 2 in L3. The results suggest that the interaction of gp120 with H3 of b12 is crucially dependent not only on a Trp residue at the apex of the H3 loop but also on a number of residues at the base of the loop. The arrangement of these residues, including aromatic side chains and side chains that hydrogen bond across the base of the loop, may rigidify H3 for penetration of the recessed CD4-binding cavity. The results further emphasize the importance to gp120 binding of a Tyr residue at the apex of the H2 loop that forms a second finger-like structure and a number of Arg residues in L1 that form a positively charged, shelf-like structure. In general, the data are consistent with the b12-gp120 interaction model previously proposed. At the gene level, somatic mutation is seen to be crucial for the generation of many of the structural features described. The Fab b12 mutants were also tested against the b12 epitope-mimic peptide B2.1, and the reactivity profile had many similarities but also significant differences from that observed for gp120. The paratope map of b12 may facilitate the design of molecules that are able to elicit b12-like activities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.