Haakenson Jeremy K, Huang Ruiqi, Smider Vaughn V
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, United States.
Front Immunol. 2018 Jun 4;9:1262. doi: 10.3389/fimmu.2018.01262. eCollection 2018.
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.
在人类和小鼠中发现的典型抗体通常具有较短的互补决定区H3（CDR H3），且结合表面一般较为扁平。然而，牛拥有一部分抗体，其CDR H3超长，可达70个氨基酸，并形成独特的“柄和旋钮”结构，其中旋钮突出于抗体表面很远的位置，在此处它有可能与具有凹形表位的抗原结合。活化诱导胞苷脱氨酶（AID）在体液免疫中使抗体库多样化方面已被证实发挥作用，并且已发现它在牛免疫球蛋白基因与抗原接触之前和之后均能诱导体细胞超突变。由于在牛中产生超长CDR H3抗体的V（D）J重排事件中可变基因和多样性基因的使用有限，因此有人提出牛超长抗体库的多样性依赖于针对编码整个旋钮区域的IGHD8 - 2基因的AID诱导突变。在本综述中，我们讨论了牛超长抗体的遗传学、结构和多样性，以及AID在创建多样化抗体库中的作用。
