ArticleAdvances in immunology2018
The Unusual Genetics and Biochemistry of Bovine Immunoglobulins.
Article in Advances in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Expression of ultralong complementarity determining region 3 and development of IgM and IgG B cell receptor repertoires in Holstein heifer calves.ImmunoHorizons · 2026Article
- Leveraging single B cell antibody platforms to develop countermeasures against animal viral diseases: recent advances and future perspectives.Frontiers in veterinary science · 2026Review
- Bovine Ultra-Long CDR H3 Specific for Bovine Rotavirus Displays Potent Virus Neutralization and Therapeutic Effects in Infected Calves.Biomolecules · 2025Article
- Immunoglobulin gene loci structure and diversity of raccoon dog (Nyctereutes procyonoides).BMC genomics · 2025Article
- Annotation of gene loci and analysis of expression diversity in sheep immunoglobulin.Frontiers in immunology · 2025Article
- Alterations in BCR heavy chain CDR3 repertoire characteristics in pediatric mycoplasma pneumoniae infection.Frontiers in cellular and infection microbiology · 2025Article
- The Janus (dual) model of immunoglobulin isotype evolution: Conservation and plasticity are the defining paradigms.Immunological reviews · 2024Review
- Investigating the IgM and IgG B Cell Receptor Repertoires and Expression of Ultralong Complementarity Determining Region 3 in Colostrum and Blood from Holstein-Friesian Cows at Calving.Animals : an open access journal from MDPI · 2024Article
- Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire.PLoS pathogens · 2024Article
- Estimates of Sequences with Ultralong and Short CDR3s in the Bovine IgM B Cell Receptor Repertoire Using the Long-read Oxford Nanopore MinION Platform.ImmunoHorizons · 2024Article
- Evaluation of the Inhibitory Potential of Synthetic Peptides Homologous to CDR3 Regions of a Monoclonal Antibody against Bothropic Venom Serine Proteases.International journal of molecular sciences · 2024Article
- Annotation and characterization of immunoglobulin loci and CDR3 polymorphism in water buffalo (Frontiers in immunology · 2024Article
- Modular design of bi- and multi-specific knob domain fusions.Frontiers in immunology · 2024Article
- The smallest functional antibody fragment: Ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Evolution of immunogenetic components encoding ultralong CDR H3.Immunogenetics · 2023Article
- Germline-Encoded Positional Cysteine Polymorphisms Enhance Diversity in Antibody Ultralong CDR H3 Regions.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Trace Minerals Supplementation with Great Impact on Beef Cattle Immunity and Health.Animals : an open access journal from MDPI · 2022Review
- Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site.Structure (London, England : 1993) · 2022Article
- Organization and Complexity of the Yak (Bos Grunniens) Immunoglobulin Loci.Frontiers in immunology · 2022Article
- Using cross-species vaccination approaches to counter emerging infectious diseases.Nature reviews. Immunology · 2021Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Antibodies are the key circulating molecules that have evolved to fight infection by the adaptive immune system of vertebrates. Typical antibodies of most species contain six complementarity-determining regions (CDRs), where the third CDR of the heavy chain (CDR H3) has the greatest diversity and often makes the most significant contact with antigen. Generally, the process of V(D)J recombination produces a vast repertoire of antibodies; multiple V, D, and J gene segments recombine with additional junctional diversity at the V-D and D-J joints, and additional combinatorial possibilities occur through heavy- and light-chain pairing. Despite these processes, the overall structure of the resulting antibody is largely conserved, and binding to antigen occurs predominantly through the CDR loops of the immunoglobulin V domains. Bovines have deviated from this general paradigm by having few VH regions and thus little germline combinatorial diversity, but their antibodies contain long CDR H3 regions, with substantial diversity generated through somatic hypermutation. A subset of the repertoire comprises antibodies with ultralong CDR H3s, which can reach over 70 amino acids in length. Structurally, these unusual antibodies form a β-ribbon "stalk" and disulfide-bonded "knob" that protrude far from the antibody surface. These long CDR H3s allow cows to mount a particularly robust immune response when immunized with viral antigens, particularly to broadly neutralizing epitopes on a stabilized HIV gp140 trimer, which has been a challenge for other species. The unusual genetics and structural biology of cows provide for a unique paradigm for creation of immune diversity and could enable generation of antibodies against especially challenging targets and epitopes.
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Registered trials
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