A comprehensive analysis of immunoglobulin heavy chain genes in the Bactrian camel (Camelus bactrianus)

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Heavy chain only antibodies (HCAbs) represent a rare type of antibody that is devoid of light chains and the CH1 domain that have been reported in cartilaginous fish and camelids. By analyzing transcript data and genome sequences, we conducted a comprehensive analysis of Bactrian camel immunoglobulin heavy chain genes. Based on the transcript data, one μ gene, five γ genes, one α gene and one ϵ gene were found. Additionally, the variable region of HCAbs (VHH) and the conventional antibodies (VH) sequences associated with the γ3, γ1a/b and μ genes were amplified. Based on these genome sequences, seven DH, six JH, μ, γ2a, γ2c, α, and ϵ genes and a portion of a γ3 gene were observed. Different Kozak sequences within different VH families were found in our analysis, and the variability index differed between the VHH3 and VH3 families. Phylogenetic analysis of the constant regions of the camelid immunoglobulin genes indicates that these genes appeared before the evolutionary divergence of Bactrian camels and dromedaries.

Most cited references 23

Record: found
Abstract: found
Article: not found

Sequence and structure of VH domain from naturally occurring camel heavy chain immunoglobulins lacking light chains.

S. Muyldermans, T. Atarhouch, J. Saldanha … (1994)

We cloned 17 different PCR fragments encoding VH genes of camel (Camelus dromedarius). These clones were derived from the camel heavy chain immunoglobulins lacking the light chain counterpart of normal immunoglobulins. Insight into the camel VH sequences and structure may help the development of single domain antibodies. The most remarkable difference in the camel VH, consistent with the absence of the VL interaction, is the substitution of the conserved Leu45 by an Arg or Cys. Another noteworthy substitution is the Leu11 to Ser. This amino acid normally interacts with the CH1 domain, a domain missing in the camel heavy chain immunoglobulins. The nature of these substitutions agrees with the increased solubility behavior of an isolated camel VH domain. The VH domains of the camels are also characterized by a long CDR3, possibly compensating for the absence of the VL contacts with the antigen. The CDR3 lacks the salt bridge between Arg94 and Asp101. However, the frequent occurrence of additional Cys residues in both the CDR1 and CDR3 might lead to the formation of a second internal disulfide bridge, thereby stabilizing the CDR structure as in the DAW antibody. Within CDRs of the camel VH domains we observe a broad size distribution and a different amino acid pattern compared with the mouse or human VH. Therefore the camel hypervariable regions might adopt structures which differ substantially from the known canonical structures, thereby increasing the repertoire of the camel antigen binding sites within a VH.

0 comments Cited 127 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Recognition of antigens by single-domain antibody fragments: the superfluous luxury of paired domains.

Serge Muyldermans, Christian Cambillau, Lode Wyns (2001)

The antigen-binding site of antibodies from vertebrates is formed by combining the variable domains of a heavy chain (VH) and a light chain (VL). However, antibodies from camels and llamas are an important exception to this in that their sera contain, in addition, a unique kind of antibody that is formed by heavy chains only. The antigen-binding site of these antibodies consists of one single domain, referred to as VHH. This article reviews the mutations and structural adaptations that have taken place to reshape a VH of a VH-VL pair into a single-domain VHH with retention of a sufficient variability. The VHH has a potent antigen-binding capacity and provides the advantage of interacting with novel epitopes that are inaccessible to conventional VH-VL pairs.

0 comments Cited 77 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Comparison of llama VH sequences from conventional and heavy chain antibodies.

K B Vu, M Ghahroudi, L Wyns … (2015)

Forty different PCR clones encoding a llama variable heavy chain domain were analysed. The majority of these clones are derived from heavy-chain antibody cDNA in which the entire CH1 exon is absent. It appears from the amino acid within the VHH framework 1 and 3 that all the llama clones belong to the VH III family. However, the individual llama VHH sequences differ more substantially from each other than expected for members of the same family. Several remarkable amino acid substitutions in the framework 2 hinder the proper association of the VL. However, they lay the foundation for the secretion from the endoplasmic reticulum and good solubility behaviour of llama H2 antibodies. The repertoire of the llama VHHs may be extensive due to the presence of a long CDR3-loop, often constrained by a disulfide bridge and the occurrence of H1 and H2 loop conformations not yet encountered in mice or human VHs. The variability plot of the amino acids in the VHH shows that the first hypervariable region coincides with the structural H1 loop in contrast to the situation found in mice and man where the CDR1 and H1 are slightly offset. We propose that the amino acids of the llama H1 loop participate actively in the antigen binding. All these observations are characteristic for the llama VHHs of the homodimeric heavy-chain H2 antibodies, but are not maintained in the llama clones from conventional heterotetrameric H2L2 immunoglobulins.

0 comments Cited 68 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Front. Agr. Sci. Eng.

Journal ID (pmc): FASE

Journal ID (publisher-id): CN10-1204/S

Title: Frontiers of Agricultural Science and Engineering

Publisher: Higher Education Press (4 Huixin Dongjie, Chaoyang District, Beijing 100029, China )

ISSN (Print): 2095-7505

Publication date (Print): 2015

Volume: 2

Issue: 3

Pages: 249-259

Affiliations

[1]1. Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China

[2]2. State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China

[3]3. Laboratory of Animal Molecular Genetics, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Taian 271018, China

[4]4. Key Laboratory of Animal Genetics, Breeding and Reproduction, Inner Mongolia Agricultural University, Hohhot 010018, China

[5]5. Bioyong Technology Inc., Beijing 100080, China

Author notes

13969675699@126.com

renlm@cau.edu.cn

Article

DOI: 10.15302/J-FASE-2015056

SO-VID: ef8d7778-f68d-4c50-a855-76ff14852c62

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

A comprehensive analysis of immunoglobulin heavy chain genes in the Bactrian camel ( Camelus bactrianus)

Read this article at

Abstract

Most cited references 23

Sequence and structure of VH domain from naturally occurring camel heavy chain immunoglobulins lacking light chains.

Recognition of antigens by single-domain antibody fragments: the superfluous luxury of paired domains.

Comparison of llama VH sequences from conventional and heavy chain antibodies.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 658

Cited by 1

Most referenced authors 553