ArticleNature communications2023
Complement is activated by elevated IgG3 hexameric platforms and deposits C4b onto distinct antibody domains.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Complement Dysregulation in Kidney Diseases: Mechanisms, Biomarkers, and Emerging Targeted Therapies.International journal of molecular sciences · 2026Review
- Complement-mediated ADCP as a distinct and finite cytotoxic mechanism of monoclonal antibodies.Frontiers in immunology · 2026Article
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- AChR Autoantibody Pathogenic Properties Are Heterogeneously Distributed and Undergo Temporal Changes Among Patients With Myasthenia Gravis.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Anti-pan-neurofascin IgG3: insights about an emerging autoimmune nodoparanodopathy.Arquivos de neuro-psiquiatria · 2025Review
- Modulation of immunoglobulin G oligomerization by variable domain glycans: A mechanism to regulate complement activation.PNAS nexus · 2025Article
- A Kinetic Model of Antigen-Dependent IgG Oligomerization and Complement Binding.Small science · 2025Article
- The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications.Signal transduction and targeted therapy · 2025Review
- Article
- Functional and phenotypic profiles of HLA-specific antibodies in relation to antibody-mediated kidney transplant rejection.Human immunology · 2025Article
- Acquired drivers of C3 glomerulopathy.Clinical kidney journal · 2025Review
- Review
- Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial.Nature communications · 2025Article
- Reflecting on chiral chimeric cancer and microbes: ambidextrous metabolism-the real danger?Frontiers in cell and developmental biology · 2025Article
- Article
- Complement activation by IgG subclasses is governed by their ability to oligomerize upon antigen binding.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Heterotrimeric collagen helix with high specificity of assembly results in a rapid rate of folding.Nature chemistry · 2024Article
- Agnostic B cell selection approach identifies antibodies against K. pneumoniae that synergistically drive complement activation.Nature communications · 2024Article
- Structural basis for surface activation of the classical complement cascade by the short pentraxin C-reactive protein.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IgG3 is unique among the IgG subclasses due to its extended hinge, allotypic diversity and enhanced effector functions, including highly efficient pathogen neutralisation and complement activation. It is also underrepresented as an immunotherapeutic candidate, partly due to a lack of structural information. Here, we use cryoEM to solve structures of antigen-bound IgG3 alone and in complex with complement components. These structures reveal a propensity for IgG3-Fab clustering, which is possible due to the IgG3-specific flexible upper hinge region and may maximise pathogen neutralisation by forming high-density antibody arrays. IgG3 forms elevated hexameric Fc platforms that extend above the protein corona to maximise binding to receptors and the complement C1 complex, which here adopts a unique protease conformation that may precede C1 activation. Mass spectrometry reveals that C1 deposits C4b directly onto specific IgG3 residues proximal to the Fab domains. Structural analysis shows this to be caused by the height of the C1-IgG3 complex. Together, these data provide structural insights into the role of the unique IgG3 extended hinge, which will aid the development and design of upcoming immunotherapeutics based on IgG3.
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