Alternative Recognition of the Conserved Stem Epitope in Influenza A Virus Hemagglutinin by a VH3-30-Encoded Heterosubtypic Antibody
Identifieur interne : 000A32 ( Ncbi/Curation ); précédent : 000A31; suivant : 000A33Alternative Recognition of the Conserved Stem Epitope in Influenza A Virus Hemagglutinin by a VH3-30-Encoded Heterosubtypic Antibody
Auteurs : Arkadiusz Wyrzucki [Suisse] ; Cyrille Dreyfus [États-Unis] ; Ines Kohler [Suisse] ; Marco Steck [Suisse] ; Ian A. Wilson [États-Unis] ; Lars Hangartner [Suisse]Source :
- Journal of Virology [ 0022-538X ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (génétique), Anticorps antiviraux (immunologie), Cartographie épitopique, Chaines lourdes des immunoglobulines (génétique), Chaines lourdes des immunoglobulines (immunologie), Glycoprotéine hémagglutinine du virus influenza (), Glycoprotéine hémagglutinine du virus influenza (génétique), Glycoprotéine hémagglutinine du virus influenza (immunologie), Grippe humaine (immunologie), Grippe humaine (virologie), Humains, Modèles moléculaires, Souris, Sous-type H1N1 du virus de la grippe A (), Sous-type H1N1 du virus de la grippe A (génétique), Sous-type H1N1 du virus de la grippe A (immunologie), Sous-type H2N2 du virus de la grippe A (), Sous-type H2N2 du virus de la grippe A (génétique), Sous-type H2N2 du virus de la grippe A (immunologie), Séquence conservée, Séquence d'acides aminés, Virus de la grippe A (), Virus de la grippe A (génétique), Virus de la grippe A (immunologie), Épitopes (), Épitopes (génétique), Épitopes (immunologie).
- MESH :
- génétique : Anticorps antiviraux, Chaines lourdes des immunoglobulines, Glycoprotéine hémagglutinine du virus influenza, Sous-type H1N1 du virus de la grippe A, Sous-type H2N2 du virus de la grippe A, Virus de la grippe A, Épitopes.
- immunologie : Anticorps antiviraux, Chaines lourdes des immunoglobulines, Glycoprotéine hémagglutinine du virus influenza, Grippe humaine, Sous-type H1N1 du virus de la grippe A, Sous-type H2N2 du virus de la grippe A, Virus de la grippe A, Épitopes.
- virologie : Grippe humaine.
- Animaux, Cartographie épitopique, Glycoprotéine hémagglutinine du virus influenza, Humains, Modèles moléculaires, Souris, Sous-type H1N1 du virus de la grippe A, Sous-type H2N2 du virus de la grippe A, Séquence conservée, Séquence d'acides aminés, Virus de la grippe A, Épitopes.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antibodies, Viral (genetics), Antibodies, Viral (immunology), Conserved Sequence, Epitope Mapping, Epitopes (chemistry), Epitopes (genetics), Epitopes (immunology), Hemagglutinin Glycoproteins, Influenza Virus (chemistry), Hemagglutinin Glycoproteins, Influenza Virus (genetics), Hemagglutinin Glycoproteins, Influenza Virus (immunology), Humans, Immunoglobulin Heavy Chains (genetics), Immunoglobulin Heavy Chains (immunology), Influenza A Virus, H1N1 Subtype (chemistry), Influenza A Virus, H1N1 Subtype (genetics), Influenza A Virus, H1N1 Subtype (immunology), Influenza A Virus, H2N2 Subtype (chemistry), Influenza A Virus, H2N2 Subtype (genetics), Influenza A Virus, H2N2 Subtype (immunology), Influenza A virus (chemistry), Influenza A virus (genetics), Influenza A virus (immunology), Influenza, Human (immunology), Influenza, Human (virology), Mice, Models, Molecular.
- MESH :
- chemical , chemistry : Epitopes, Hemagglutinin Glycoproteins, Influenza Virus.
- chemical , genetics : Antibodies, Viral, Epitopes, Hemagglutinin Glycoproteins, Influenza Virus, Immunoglobulin Heavy Chains.
- chemical , immunology : Antibodies, Viral, Epitopes, Hemagglutinin Glycoproteins, Influenza Virus, Immunoglobulin Heavy Chains.
- chemistry : Influenza A Virus, H1N1 Subtype, Influenza A Virus, H2N2 Subtype, Influenza A virus.
- genetics : Influenza A Virus, H1N1 Subtype, Influenza A Virus, H2N2 Subtype, Influenza A virus.
- immunology : Influenza A Virus, H1N1 Subtype, Influenza A Virus, H2N2 Subtype, Influenza A virus, Influenza, Human.
- virology : Influenza, Human.
- Amino Acid Sequence, Animals, Conserved Sequence, Epitope Mapping, Humans, Mice, Models, Molecular.
Abstract
A human monoclonal heterosubtypic antibody, MAb 3.1, with its heavy chain encoded by VH3-30, was isolated using phage display with immobilized hemagglutinin (HA) from influenza virus A/Japan/305/1957(H2N2) as the target. Antibody 3.1 potently neutralizes influenza viruses from the H1a clade (i.e., H1, H2, H5, H6) but has little neutralizing activity against the H1b clade. Its crystal structure in complex with HA from a pandemic H1N1 influenza virus, A/South Carolina/1/1918(H1N1), revealed that like other heterosubtypic anti-influenza virus antibodies, MAb 3.1 contacts a hydrophobic groove in the HA stem, primarily using its heavy chain. However, in contrast to the closely related monoclonal antibody (Mab) FI6 that relies heavily on HCDR3 for binding, MAb 3.1 utilizes residues from HCDR1, HCDR3, and framework region 3 (FR3). Interestingly, HCDR1 of MAb 3.1 adopts an α-helical conformation and engages in hydrophobic interactions with the HA very similar to those of the
Url:
DOI: 10.1128/JVI.00178-14
PubMed: 24719426
PubMed Central: 4054347
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PMC:4054347Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Antibodies, Viral (genetics)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Conserved Sequence</term>
<term>Epitope Mapping</term>
<term>Epitopes (chemistry)</term>
<term>Epitopes (genetics)</term>
<term>Epitopes (immunology)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (chemistry)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (immunology)</term>
<term>Humans</term>
<term>Immunoglobulin Heavy Chains (genetics)</term>
<term>Immunoglobulin Heavy Chains (immunology)</term>
<term>Influenza A Virus, H1N1 Subtype (chemistry)</term>
<term>Influenza A Virus, H1N1 Subtype (genetics)</term>
<term>Influenza A Virus, H1N1 Subtype (immunology)</term>
<term>Influenza A Virus, H2N2 Subtype (chemistry)</term>
<term>Influenza A Virus, H2N2 Subtype (genetics)</term>
<term>Influenza A Virus, H2N2 Subtype (immunology)</term>
<term>Influenza A virus (chemistry)</term>
<term>Influenza A virus (genetics)</term>
<term>Influenza A virus (immunology)</term>
<term>Influenza, Human (immunology)</term>
<term>Influenza, Human (virology)</term>
<term>Mice</term>
<term>Models, Molecular</term>
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<term>Anticorps antiviraux (génétique)</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Cartographie épitopique</term>
<term>Chaines lourdes des immunoglobulines (génétique)</term>
<term>Chaines lourdes des immunoglobulines (immunologie)</term>
<term>Glycoprotéine hémagglutinine du virus influenza ()</term>
<term>Glycoprotéine hémagglutinine du virus influenza (génétique)</term>
<term>Glycoprotéine hémagglutinine du virus influenza (immunologie)</term>
<term>Grippe humaine (immunologie)</term>
<term>Grippe humaine (virologie)</term>
<term>Humains</term>
<term>Modèles moléculaires</term>
<term>Souris</term>
<term>Sous-type H1N1 du virus de la grippe A ()</term>
<term>Sous-type H1N1 du virus de la grippe A (génétique)</term>
<term>Sous-type H1N1 du virus de la grippe A (immunologie)</term>
<term>Sous-type H2N2 du virus de la grippe A ()</term>
<term>Sous-type H2N2 du virus de la grippe A (génétique)</term>
<term>Sous-type H2N2 du virus de la grippe A (immunologie)</term>
<term>Séquence conservée</term>
<term>Séquence d'acides aminés</term>
<term>Virus de la grippe A ()</term>
<term>Virus de la grippe A (génétique)</term>
<term>Virus de la grippe A (immunologie)</term>
<term>Épitopes ()</term>
<term>Épitopes (génétique)</term>
<term>Épitopes (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antibodies, Viral</term>
<term>Epitopes</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
<term>Immunoglobulin Heavy Chains</term>
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<term>Epitopes</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
<term>Immunoglobulin Heavy Chains</term>
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<term>Influenza A Virus, H2N2 Subtype</term>
<term>Influenza A virus</term>
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<term>Influenza A Virus, H2N2 Subtype</term>
<term>Influenza A virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Chaines lourdes des immunoglobulines</term>
<term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
<term>Sous-type H2N2 du virus de la grippe A</term>
<term>Virus de la grippe A</term>
<term>Épitopes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Chaines lourdes des immunoglobulines</term>
<term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Grippe humaine</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
<term>Sous-type H2N2 du virus de la grippe A</term>
<term>Virus de la grippe A</term>
<term>Épitopes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term>
<term>Influenza A Virus, H2N2 Subtype</term>
<term>Influenza A virus</term>
<term>Influenza, Human</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Grippe humaine</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Influenza, Human</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Conserved Sequence</term>
<term>Epitope Mapping</term>
<term>Humans</term>
<term>Mice</term>
<term>Models, Molecular</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cartographie épitopique</term>
<term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Humains</term>
<term>Modèles moléculaires</term>
<term>Souris</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
<term>Sous-type H2N2 du virus de la grippe A</term>
<term>Séquence conservée</term>
<term>Séquence d'acides aminés</term>
<term>Virus de la grippe A</term>
<term>Épitopes</term>
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<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>A human monoclonal heterosubtypic antibody, MAb 3.1, with its heavy chain encoded by V<sub>H</sub>
3-30, was isolated using phage display with immobilized hemagglutinin (HA) from influenza virus A/Japan/305/1957(H2N2) as the target. Antibody 3.1 potently neutralizes influenza viruses from the H1a clade (i.e., H1, H2, H5, H6) but has little neutralizing activity against the H1b clade. Its crystal structure in complex with HA from a pandemic H1N1 influenza virus, A/South Carolina/1/1918(H1N1), revealed that like other heterosubtypic anti-influenza virus antibodies, MAb 3.1 contacts a hydrophobic groove in the HA stem, primarily using its heavy chain. However, in contrast to the closely related monoclonal antibody (Mab) FI6 that relies heavily on HCDR3 for binding, MAb 3.1 utilizes residues from HCDR1, HCDR3, and framework region 3 (FR3). Interestingly, HCDR1 of MAb 3.1 adopts an α-helical conformation and engages in hydrophobic interactions with the HA very similar to those of the <italic>de novo in silico</italic>
-designed and affinity-matured synthetic protein HB36.3. These findings improve our understanding of the molecular requirements for binding to the conserved epitope in the stem of the HA protein and, therefore, aid the development of more universal influenza vaccines targeting these epitopes.</p>
<p><bold>IMPORTANCE</bold>
Influenza viruses rapidly evade preexisting immunity by constantly altering the immunodominant neutralizing antibody epitopes (antigenic drift) or by acquiring new envelope serotypes (antigenic shift). As a consequence, the majority of antibodies elicited by immunization or infection protect only against the immunizing or closely related strains. Here, we describe a novel monoclonal antibody that recognizes the conserved heterosubtypic epitope in the stem of influenza A virus hemagglutinin. This antibody, referred to as MAb 3.1, recognizes its epitope in a manner that resembles recognition of a similar epitope by the <italic>de novo in silico</italic>
-designed and affinity-matured synthetic protein HB36.3. Thus, besides providing novel insights into the molecular interactions between heterosubtypic antibodies and influenza virus hemagglutinin, MAb 3.1 demonstrates that <italic>de novo in silico</italic>
-designed and affinity-matured synthetic proteins can foretell naturally selected antibody binding. This knowledge will aid development of a pan-influenza virus vaccine.</p>
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