MersV1, Main, Exploration, bibRecord, 001733

Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

Identifieur interne : 001733 ( Main/Exploration ); précédent : 001732; suivant : 001734

Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

Auteurs : Tianlei Ying [République populaire de Chine] ; Ponraj Prabakaran [États-Unis] ; Lanying Du [États-Unis] ; Wei Shi ; Yang Feng ; Yanping Wang ; Lingshu Wang ; Wei Li [République populaire de Chine] ; Shibo Jiang [République populaire de Chine, États-Unis] ; Dimiter S. Dimitrov ; Tongqing Zhou

Source :

Nature Communications [ 2041-1723 ] ; 2015.

RBID : PMC:4571279

Descripteurs français

English descriptors

KwdEn :
- Alleles, Antibodies, Neutralizing (genetics), Antibodies, Neutralizing (immunology), Antibodies, Viral (genetics), Antibodies, Viral (immunology), Crystallization, Crystallography, X-Ray, Epitopes, Genes, Immunoglobulin Heavy Chain (genetics), Genes, Immunoglobulin Heavy Chain (immunology), Humans, Immunoglobulin G (genetics), Immunoglobulin G (immunology), Middle East Respiratory Syndrome Coronavirus (immunology), Somatic Hypermutation, Immunoglobulin (genetics), Somatic Hypermutation, Immunoglobulin (immunology), V(D)J Recombination (genetics), V(D)J Recombination (immunology).
MESH :
- chemical , genetics : Antibodies, Neutralizing, Antibodies, Viral, Immunoglobulin G.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Immunoglobulin G.
- genetics : Genes, Immunoglobulin Heavy Chain, Somatic Hypermutation, Immunoglobulin, V(D)J Recombination.
- immunology : Genes, Immunoglobulin Heavy Chain, Middle East Respiratory Syndrome Coronavirus, Somatic Hypermutation, Immunoglobulin, V(D)J Recombination.
- Alleles, Crystallization, Crystallography, X-Ray, Epitopes, Humans.

Abstract

The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (∼36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.

Supplementary information

The online version of this article (doi:10.1038/ncomms9223) contains supplementary material, which is available to authorized users.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571279

DOI: 10.1038/ncomms9223
PubMed: 26370782
PubMed Central: 4571279

Affiliations:

Le document en format XML

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<term>Antibodies, Neutralizing (genetics)</term>
<term>Antibodies, Neutralizing (immunology)</term>
<term>Antibodies, Viral (genetics)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Crystallization</term>
<term>Crystallography, X-Ray</term>
<term>Epitopes</term>
<term>Genes, Immunoglobulin Heavy Chain (genetics)</term>
<term>Genes, Immunoglobulin Heavy Chain (immunology)</term>
<term>Humans</term>
<term>Immunoglobulin G (genetics)</term>
<term>Immunoglobulin G (immunology)</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Somatic Hypermutation, Immunoglobulin (genetics)</term>
<term>Somatic Hypermutation, Immunoglobulin (immunology)</term>
<term>V(D)J Recombination (genetics)</term>
<term>V(D)J Recombination (immunology)</term>
</keywords>
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<term>Anticorps antiviraux (génétique)</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps neutralisants (génétique)</term>
<term>Anticorps neutralisants (immunologie)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Cristallisation</term>
<term>Cristallographie aux rayons X</term>
<term>Gènes de chaine lourde d'immunoglobuline (génétique)</term>
<term>Gènes de chaine lourde d'immunoglobuline (immunologie)</term>
<term>Humains</term>
<term>Hypermutation somatique des gènes des immunoglobulines (génétique)</term>
<term>Hypermutation somatique des gènes des immunoglobulines (immunologie)</term>
<term>Immunoglobuline G (génétique)</term>
<term>Immunoglobuline G (immunologie)</term>
<term>Recombinaison V(D)J (génétique)</term>
<term>Recombinaison V(D)J (immunologie)</term>
<term>Épitopes</term>
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<term>Antibodies, Viral</term>
<term>Immunoglobulin G</term>
</keywords>
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<term>Somatic Hypermutation, Immunoglobulin</term>
<term>V(D)J Recombination</term>
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<term>Hypermutation somatique des gènes des immunoglobulines</term>
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<term>Recombinaison V(D)J</term>
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<term>Anticorps neutralisants</term>
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<term>Gènes de chaine lourde d'immunoglobuline</term>
<term>Hypermutation somatique des gènes des immunoglobulines</term>
<term>Immunoglobuline G</term>
<term>Recombinaison V(D)J</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Genes, Immunoglobulin Heavy Chain</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Somatic Hypermutation, Immunoglobulin</term>
<term>V(D)J Recombination</term>
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<keywords scheme="MESH" xml:lang="en"><term>Alleles</term>
<term>Crystallization</term>
<term>Crystallography, X-Ray</term>
<term>Epitopes</term>
<term>Humans</term>
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<keywords scheme="MESH" xml:lang="fr"><term>Allèles</term>
<term>Cristallisation</term>
<term>Cristallographie aux rayons X</term>
<term>Humains</term>
<term>Épitopes</term>
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<front><div type="abstract" xml:lang="en"><p id="Par1">The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (∼36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation <italic>in vivo</italic>
.</p>
<sec><title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/ncomms9223) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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Serveur d'exploration MERS

Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

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