Diversity in the Cow Ultralong CDR H3 Antibody Repertoire

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 an...

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Main Authors: Jeremy K. Haakenson, Ruiqi Huang, Vaughn V. Smider
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.01262/full
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author Jeremy K. Haakenson
Ruiqi Huang
Vaughn V. Smider
author_facet Jeremy K. Haakenson
Ruiqi Huang
Vaughn V. Smider
author_sort Jeremy K. Haakenson
collection DOAJ
description 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.
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spelling doaj.art-21963ece231745aca15cc2ea3f16ece32022-12-22T03:20:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-06-01910.3389/fimmu.2018.01262380945Diversity in the Cow Ultralong CDR H3 Antibody RepertoireJeremy K. HaakensonRuiqi HuangVaughn V. SmiderTypical 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.01262/fullantibodyultralong CDRH3cow immunoglobulinactivation-induced cytidine deaminaseantibody repertoire
spellingShingle Jeremy K. Haakenson
Ruiqi Huang
Vaughn V. Smider
Diversity in the Cow Ultralong CDR H3 Antibody Repertoire
Frontiers in Immunology
antibody
ultralong CDRH3
cow immunoglobulin
activation-induced cytidine deaminase
antibody repertoire
title Diversity in the Cow Ultralong CDR H3 Antibody Repertoire
title_full Diversity in the Cow Ultralong CDR H3 Antibody Repertoire
title_fullStr Diversity in the Cow Ultralong CDR H3 Antibody Repertoire
title_full_unstemmed Diversity in the Cow Ultralong CDR H3 Antibody Repertoire
title_short Diversity in the Cow Ultralong CDR H3 Antibody Repertoire
title_sort diversity in the cow ultralong cdr h3 antibody repertoire
topic antibody
ultralong CDRH3
cow immunoglobulin
activation-induced cytidine deaminase
antibody repertoire
url https://www.frontiersin.org/article/10.3389/fimmu.2018.01262/full
work_keys_str_mv AT jeremykhaakenson diversityinthecowultralongcdrh3antibodyrepertoire
AT ruiqihuang diversityinthecowultralongcdrh3antibodyrepertoire
AT vaughnvsmider diversityinthecowultralongcdrh3antibodyrepertoire