ArticleProceedings of the National Academy of Sciences of the United States of America2020
Conformational diversity facilitates antibody mutation trajectories and discrimination between foreign and self-antigens.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- The immune protection of OMP16-specific IgM against Brucella infection.BMC biology · 2026Article
- Observation of redistribution for local conformational dynamics in cross-reactive antibody design.Journal of biochemistry · 2026Article
- Humoral epitope dominance and immune imprinting by SARS-CoV-1 and SARS-CoV-2 vaccines.Immunology and cell biology · 2026Article
- Framework-mediated binding of foreign and self-glycans by IGHV4-34 antibodies.Frontiers in immunology · 2026Review
- Convergent mutation trajectories convert functional self-tolerance in IGHV4-34 B cells to genetic tolerance encoded in the antibody.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structure and dynamics of GAD65 in complex with an autoimmune polyendocrine syndrome type 2-associated autoantibody.Nature communications · 2025Article
- Antibodies and cryptographic hash functions: quantifying the specificity paradox.Frontiers in immunology · 2025Article
- Advancements in the conservation of the conformational epitope of membrane protein immunogens.Frontiers in immunology · 2025Review
- Central tolerance shapes the neutralizing B cell repertoire against a persisting virus in its natural host.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Biochemical and biophysical characterization of natural polyreactivity in antibodies.Cell reports · 2023Article
- An optimized thermodynamics integration protocol for identifying beneficial mutations in antibody design.Frontiers in immunology · 2023Article
- Role of the mechanisms for antibody repertoire diversification in monoclonal light chain deposition disorders: when a friend becomes foe.Frontiers in immunology · 2023Review
- Suppressive might of a few: T follicular regulatory cells impede auto-reactivity despite being outnumbered in the germinal centres.Frontiers in immunology · 2023Article
- Features of B Cell Responses Relevant to Allergic Disease.Journal of immunology (Baltimore, Md. : 1950) · 2022Review
- B cells in the balance: Offsetting self-reactivity avoidance with protection against foreign.Frontiers in immunology · 2022Review
- Insights Into the Host Contribution of Endocrine Associated Immune-Related Adverse Events to Immune Checkpoint Inhibition Therapy.Frontiers in oncology · 2022Review
- COVID-19, varying genetic resistance to viral disease and immune tolerance checkpoints.Immunology and cell biology · 2021Review
- Structure of Blood Coagulation Factor VIII in Complex With an Anti-C2 Domain Non-Classical, Pathogenic Antibody Inhibitor.Frontiers in immunology · 2021Article
- Structural Basis of Antibody Conformation and Stability Modulation by Framework Somatic Hypermutation.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Conformational diversity and self-cross-reactivity of antigens have been correlated with evasion from neutralizing antibody responses. We utilized single cell B cell sequencing, biolayer interferometry and X-ray crystallography to trace mutation selection pathways where the antibody response must resolve cross-reactivity between foreign and self-proteins bearing near-identical contact surfaces, but differing in conformational flexibility. Recurring antibody mutation trajectories mediate long-range rearrangements of framework (FW) and complementarity determining regions (CDRs) that increase binding site conformational diversity. These antibody mutations decrease affinity for self-antigen 19-fold and increase foreign affinity 67-fold, to yield a more than 1,250-fold increase in binding discrimination. These results demonstrate how conformational diversity in antigen and antibody does not act as a barrier, as previously suggested, but rather facilitates high affinity and high discrimination between foreign and self.
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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.