The specific variable domain of camel heavy-chain antibodies is encoded in the germline

Nguyen, Viet Khong; Muyldermans, Serge; Hamers, R.

doi:10.1006/jmbi.1997.1477

Cited by 81 publications

(62 citation statements)

References 40 publications

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“…Apparently, neither the V H H hallmark amino acids, nor the presence of a long CDR3 loop of 24 aa, caused folding problems (43). Nevertheless, the genomic organization of the V H H genes (i.e., promoter, leader signal, intron, V-exon, and recombination signal sequence) is otherwise remarkably similar to that of the conventional V H counterparts (44). It has been reasoned that V H H genes have recently evolved from conventional V H genes after the emergence of the Tylopoda (Ͼ50 million years ago), which makes it likely that both types are accommodated in the V gene cluster of the H chain locus (44).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the genomic organization of the V H H genes (i.e., promoter, leader signal, intron, V-exon, and recombination signal sequence) is otherwise remarkably similar to that of the conventional V H counterparts (44). It has been reasoned that V H H genes have recently evolved from conventional V H genes after the emergence of the Tylopoda (Ͼ50 million years ago), which makes it likely that both types are accommodated in the V gene cluster of the H chain locus (44). This is supported by the observation that both the V H and V H H gene segments appear to rearrange to the same D and J H gene segments to form either a conventional Ab or a H chain Ab (21).…”

Section: Discussionmentioning

confidence: 99%

“…The observations may be compatible if lower H chain expression levels in early B cells are taken into account and if apoptosis, which may be induced when insoluble (accumulated) H chain complexes damage the cell, occurs at a later differentiation stage. The lack of L chain in the cam mice must be the result of the failure of the dromedary H chains to associate with L chains, which arises from the difference in important residues in V H H genes compared with V H genes (44). Prohibited L chain association may act as a feedback signal that stops L chain translation.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, H chain Ab deposition on the cell surface is of key importance for the formation of the H chain Ab repertoire (63,64). The formation of H chain Abs in camelids is decided by rearrangement of a V H H gene to commonly used D and J H segments (44) and (switch?) recombination to a C␥ gene that permits the removal of C H 1 (22,24).…”

Section: Discussionmentioning

confidence: 99%

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Expression of a Dromedary Heavy Chain-Only Antibody and B Cell Development in the Mouse

Zou

Smith

Nguyen

et al. 2005

The Journal of Immunology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Expression of a Dromedary Heavy Chain-Only Antibody and B Cell Development in the Mouse

Zou

Smith

Nguyen

et al. 2005

The Journal of Immunology

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“…Estructuralmente los HCAbs carecen del dominio CH1, aunque las secuencias codificadoras están presentes. La ausencia del dominio CH1 en la molécula de Ig es a causa de una remoción post-transcripcional al exón correspondiente (Nguyen et al 1998;De Genst et al,. 2006).…”

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Caracterización de IgM, IgG Total, IgG1 y anticuerpos de cadena pesada en calostro de llamas ("Lama glama") mediante Elisa

Caggiano¹,

Saccodossi

Gentile

et al. 2014

Revista Complutense De Ciencias Veterinarias

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RESUMENObjetivos: determinar los niveles de IgM, IgG total y Anticuerpos de Cadena Pesada (HCAbs; por su sigla en inglés Heavy Chain Antibodies) (IgG2 e IgG3) en calostro de llamas y evaluar la concentración de HCAbs en relación a la IgG total y al isotipo convencional IgG1.Métodos: en este estudio se utilizaron 15 llamas preñadas, que fueron ordeñadas dentro de las primeras 24 horas post-parto. Se diseñaron ELISAs Sandwich para la cuantificación de IgM total, IgG total e IgG1. La concentración de HCAbs fue calculada mediante la diferencia entre IgG total e IgG1. (HCAbs =IgG total-IgG1).Resultados: los niveles encontrados fueron: IgM=17.02 mg/ml (DS=9.85) IgG total= 42.54 mg/ml (DS=27.79), IgG1=24.34 mg/ml (DS=13.96) y HCAbs (IgG total-IgG1)= 18.19 mg/ml (DS=15.49). Los resultados de IgG fueron consistentes en relación a lo descripto en otras especies con similar tipo de placentación. Los HCAbs representan el 43% de IgG calostral y la concentración de IgM presentó valores muy altos (dos y tres veces más elevados) que los descriptos en las especies con similar tipo de placentación.

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Unique single-domain antigen binding fragments derived from naturally occurring camel heavy-chain antibodies

Lauwereys

1999

J. Mol. Recognit.

119

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The humoral immune response of camels, dromedaries and llamas includes functional antibodies formed by two heavy chains and no light chains. The amino acid sequence of the variable domain of the naturally occurring heavy-chain antibodies reveals the necessary adaptations to compensate for the absence of the light chain. In contrast to the conventional antibodies, a large proportion of the heavy-chain antibodies acts as competitive enzyme inhibitors. Studies on the dromedary immunoglobulin genes start to shed light on the ontogeny of these heavy-chain antibodies. The presence of the heavy-chain antibodies and the possibility of immunizing a dromedary allows for the production of antigen binders consisting of a single domain only. These minimal antigen-binding fragments are well expressed in bacteria, bind the antigen with affinity in the nM range and are very stable. We expect that such camelid single domain antibodies will find their way into a number of biotechnological or medical applications. The structure of the camelid single domain is homologous to the human VH, however, the antigen-binding loop structures deviate fundamentally from the canonical structures described for human or mouse VHs. This has two additional advantages: (1) the camel or llama derived single domain antibodies might be an ideal scaffold for anti-idiotypic vaccinations; and (2) the development of smaller peptides or peptide mimetic drugs derived from of the antigen binding loops might be facilitated due to their less complex antigen binding site.

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The specific variable domain of camel heavy-chain antibodies is encoded in the germline

Cited by 81 publications

References 40 publications

Expression of a Dromedary Heavy Chain-Only Antibody and B Cell Development in the Mouse

Expression of a Dromedary Heavy Chain-Only Antibody and B Cell Development in the Mouse

Caracterización de IgM, IgG Total, IgG1 y anticuerpos de cadena pesada en calostro de llamas ("Lama glama") mediante Elisa

Unique single-domain antigen binding fragments derived from naturally occurring camel heavy-chain antibodies

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