ArticleProteins2015
Key mutations stabilize antigen-binding conformation during affinity maturation of a broadly neutralizing influenza antibody lineage.
Article in Proteins, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Elicitation of stem-directed antibodies in rhesus macaques by a conventional hemagglutinin immunogen.bioRxiv : the preprint server for biology · 2026Article
- Machine Learning Approaches for Interpretable Antibody Property Prediction Using Structural Data.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Fluorescence-barcoded cell lines stably expressing membrane-anchored influenza neuraminidases.Vaccine · 2025Article
- An intranasally administered IgM protects against antigenically distinct subtypes of influenza A viruses.Nature communications · 2025Article
- Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework.Antibodies (Basel, Switzerland) · 2024Article
- Article
- Antigen binding by conformational selection in near-germline antibodies.The Journal of biological chemistry · 2022Article
- Binding affinity landscapes constrain the evolution of broadly neutralizing anti-influenza antibodies.eLife · 2021Article
- Influenza Virus and SARS-CoV-2 Vaccines.Journal of immunology (Baltimore, Md. : 1950) · 2021Review
- Structural Basis of Antibody Conformation and Stability Modulation by Framework Somatic Hypermutation.Frontiers in immunology · 2021Article
- Identification of Structurally Related Antibodies in Antibody Sequence Databases Using Rosetta-Derived Position-Specific Scoring.Structure (London, England : 1993) · 2020Article
- Effects of a remote mutation from the contact paratope on the structure of CDR-H3 in the anti-HIV neutralizing antibody PG16.Scientific reports · 2019Article
- Affinity maturation in a human humoral response to influenza hemagglutinin.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Role of antibody heavy and light chain interface residues in affinity maturation of binding to HIV envelope glycoprotein.Molecular systems design & engineering · 2019Article
- Peptide Mapping, In Silico and In Vivo Analysis of Allergenic Sorghum Profilin Peptides.Medicina (Kaunas, Lithuania) · 2019Article
- Article
- NaPhysical chemistry chemical physics : PCCP · 2019Article
- Multistate design of influenza antibodies improves affinity and breadth against seasonal viruses.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms.Toxins · 2019Article
- Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires.Immunity · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Affinity maturation, the process in which somatic hypermutation and positive selection generate antibodies with increasing affinity for an antigen, is pivotal in acquired humoral immunity. We have studied the mechanism of affinity gain in a human B-cell lineage in which two main maturation pathways, diverging from a common ancestor, lead to three mature antibodies that neutralize a broad range of H1 influenza viruses. Previous work showed that increased affinity in the mature antibodies derives primarily from stabilization of the CDR H3 loop in the antigen-binding conformation. We have now used molecular dynamics simulations and existing crystal structures to identify potentially key maturation mutations, and we have characterized their effects on the CDR H3 loop and on antigen binding using further simulations and experimental affinity measurements, respectively. In the two maturation pathways, different contacts between light and heavy chains stabilize the CDR H3 loop. As few as two single-site mutations in each pathway can confer substantial loop stability, but none of them confers experimentally detectable stability on its own. Our results support models of the germinal center reaction in which two or more mutations can occur without concomitant selection and show how divergent pathways have yielded functionally equivalent antibodies.
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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.