The Unusual Genetics and Biochemistry of Bovine Immunoglobulins
| Autor: | Jeremy K. Haakenson, Vaughn V. Smider, Ian A. Wilson, Michael F. Criscitiello, Thaddeus C. Deiss, Robyn L. Stanfield |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Immunoglobulins Somatic hypermutation chemical and pharmacologic phenomena Article Epitope Epitopes 03 medical and health sciences Antigen Antibody Repertoire Animals Humans Genetics Vaccines biology Antibody Diversity Acquired immune system Antibodies Neutralizing Complementarity Determining Regions Junctional diversity 030104 developmental biology Antibody Formation biology.protein Cattle Antibody |
| DOI: | 10.1016/bs.ai.2017.12.004 |
| Popis: | 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 seventy 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 immunizied 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. |
| Databáze: | OpenAIRE |
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