Diversity in the Cow Ultralong CDR H3 Antibody Repertoire. 2018

Jeremy K Haakenson, and Ruiqi Huang, and Vaughn V Smider
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, United States.

Typical antibodies found in humans and mice usually have short CDR H3s and generally flat binding surfaces. However, cows possess a subset of antibodies with ultralong CDR H3s that can range up to 70 amino acids and form a unique "stalk and knob" structure, with the knob protruding far out of the antibody surface, where it has the potential to bind antigens with concave epitopes. Activation-induced cytidine deaminase (AID) has a proven role in diversifying antibody repertoires in humoral immunity, and it has been found to induce somatic hypermutation in bovine immunoglobulin genes both before and after contact with antigen. Due to limited use of variable and diversity genes in the V(D)J recombination events that produce ultralong CDR H3 antibodies in cows, the diversity in the bovine ultralong antibody repertoire has been proposed to rely on AID-induced mutations targeted to the IGHD8-2 gene that encodes the entire knob region. In this review, we discuss the genetics, structures, and diversity of bovine ultralong antibodies, as well as the role of AID in creating a diverse antibody repertoire.

UI MeSH Term Description Entries
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000906 Antibodies Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
D000916 Antibody Diversity The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS. Germ Line Theory,Antibody Diversities,Diversities, Antibody,Diversity, Antibody,Germ Line Theories,Theories, Germ Line,Theory, Germ Line
D000941 Antigens Substances that are recognized by the immune system and induce an immune reaction. Antigen
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014644 Genetic Variation Genotypic differences observed among individuals in a population. Genetic Diversity,Variation, Genetic,Diversity, Genetic,Diversities, Genetic,Genetic Diversities,Genetic Variations,Variations, Genetic

Related Publications

Jeremy K Haakenson, and Ruiqi Huang, and Vaughn V Smider
December 2022, Journal of immunology (Baltimore, Md. : 1950),
Jeremy K Haakenson, and Ruiqi Huang, and Vaughn V Smider
June 2016, Current opinion in structural biology,
Jeremy K Haakenson, and Ruiqi Huang, and Vaughn V Smider
September 2023, Proceedings of the National Academy of Sciences of the United States of America,
Jeremy K Haakenson, and Ruiqi Huang, and Vaughn V Smider
February 2015, Structure (London, England : 1993),
Jeremy K Haakenson, and Ruiqi Huang, and Vaughn V Smider
December 1999, Proteins,
Jeremy K Haakenson, and Ruiqi Huang, and Vaughn V Smider
November 2010, Journal of immunology (Baltimore, Md. : 1950),
Jeremy K Haakenson, and Ruiqi Huang, and Vaughn V Smider
April 2016, Protein science : a publication of the Protein Society,
Jeremy K Haakenson, and Ruiqi Huang, and Vaughn V Smider
January 2018, Frontiers in immunology,
Jeremy K Haakenson, and Ruiqi Huang, and Vaughn V Smider
January 2019, Molecular immunology,
Copied contents to your clipboard!