ArticlePLoS pathogens2014
Ontogeny of recognition specificity and functionality for the broadly neutralizing anti-HIV antibody 4E10.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Integrating Exposures and Multi-Omics in the Boston Birth Cohort to Elucidate Immune Development across the Life Course: Rationale and Study Design.Precision nutrition · 2025Article
- Comprehensive phage display viral antibody profiling using VirScan: potential applications in chronic immune-mediated disease.Journal of virology · 2024Review
- Defining and Studying B Cell Receptor and TCR Interactions.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
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- Effects of HLA single chain trimer design on peptide presentation and stability.Frontiers in immunology · 2023Article
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- Mutational fitness landscapes reveal genetic and structural improvement pathways for a vaccine-elicited HIV-1 broadly neutralizing antibody.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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- An MPER antibody neutralizes HIV-1 using germline features shared among donors.Nature communications · 2019Article
- Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01.Cell host & microbe · 2019Article
- Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies.Nature communications · 2019Article
- PhIP-Seq characterization of serum antibodies using oligonucleotide-encoded peptidomes.Nature protocols · 2018Article
- Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity.Cell reports · 2018Article
- Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies.eLife · 2018Article
- Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies.Cell reports · 2017Article
- Germline-targeting immunogens.Immunological reviews · 2017Review
- Somatic Hypermutation-Induced Changes in the Structure and Dynamics of HIV-1 Broadly Neutralizing Antibodies.Structure (London, England : 1993) · 2016Article
- Article
- The Broadly Neutralizing, Anti-HIV Antibody 4E10: an Open and Shut Case?Journal of virology · 2016Article
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12 authors.
Funding
Abstract
The process of antibody ontogeny typically improves affinity, on-rate, and thermostability, narrows polyspecificity, and rigidifies the combining site to the conformer optimal for binding from the broader ensemble accessible to the precursor. However, many broadly-neutralizing anti-HIV antibodies incorporate unusual structural elements and recognition specificities or properties that often lead to autoreactivity. The ontogeny of 4E10, an autoreactive antibody with unexpected combining site flexibility, was delineated through structural and biophysical comparisons of the mature antibody with multiple potential precursors. 4E10 gained affinity primarily by off-rate enhancement through a small number of mutations to a highly conserved recognition surface. Controverting the conventional paradigm, the combining site gained flexibility and autoreactivity during ontogeny, while losing thermostability, though polyspecificity was unaffected. Details of the recognition mechanism, including inferred global effects due to 4E10 binding, suggest that neutralization by 4E10 may involve mechanisms beyond simply binding, also requiring the ability of the antibody to induce conformational changes distant from its binding site. 4E10 is, therefore, unlikely to be re-elicited by conventional vaccination strategies.
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