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Naturally Occurring Antibodies in Humans Can Neutralize a Variety of Influenza Virus Strains, Including H3, H1, H2, and H5

Identifieur interne : 000D60 ( Main/Exploration ); précédent : 000D59; suivant : 000D61

Naturally Occurring Antibodies in Humans Can Neutralize a Variety of Influenza Virus Strains, Including H3, H1, H2, and H5

Auteurs : Nobuko Ohshima [Japon] ; Yoshitaka Iba [Japon] ; Ritsuko Kubota-Koketsu [Japon] ; Yoshizo Asano [Japon] ; Yoshinobu Okuno [Japon] ; Yoshikazu Kurosawa [Japon]

Source :

RBID : Pascal:11-0465000

Descripteurs français

English descriptors

Abstract

Influenza A viruses are classified into 16 subtypes according to the serotypes of hemagglutinin (HA). It is generally thought that neutralizing antibodies (Abs) are not broadly cross-reactive among HA subtypes. We examined the repertoire of neutralizing Abs against influenza viruses in humans. B lymphocytes were collected from donors by apheresis, and Ab libraries were constructed by using phage-display technology. Anti-HA clones were isolated by screening with H3N2 viruses. Their binding activity was examined, and four kinds of Abs showing broad strain specificity were identified from one donor. Two of the Abs, F045-092 and F026-427, were extensively analyzed. They neutralized not only H3N2 but also H1N1, H2N2, and H5N1 viruses, although the activities were largely varied. Flow cytometry suggested that they have the ability to bind to HA and HA1 artificially expressed on the cell surface. They show hemagglutination inhibition activity and do not compete with C179, an Ab thought to bind to the stalk region. F045-092 competes with Abs that recognize sites A and B for binding to HA. Furthermore, the serine at residue 136 in site A could be a part of the epitope. Thus, it is likely that F045-092 and F026-427 bind to a conserved epitope in the head region formed by HA1. Interestingly, while the VH1-69 gene can encode MAbs against the HA stem that are group 1 specific, F045-092 and its relatives that recognize the head region also use VH1-69. The possible epitope recognized by these clones is discussed.

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<term>Antibodies, Neutralizing (immunology)</term>
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<term>Antibody</term>
<term>B-Lymphocytes (immunology)</term>
<term>Cross Reactions</term>
<term>Epitopes (immunology)</term>
<term>Hemagglutination Inhibition Tests</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (immunology)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (metabolism)</term>
<term>Human</term>
<term>Humans</term>
<term>Influenza A virus</term>
<term>Influenza A virus (immunology)</term>
<term>Molecular Sequence Data</term>
<term>Neutralization Tests</term>
<term>Peptide Library</term>
<term>Protein Binding</term>
<term>Sequence Analysis, DNA</term>
<term>Strain</term>
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<term>Analyse de séquence d'ADN</term>
<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps neutralisants (immunologie)</term>
<term>Banque de peptides</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine hémagglutinine du virus influenza (immunologie)</term>
<term>Glycoprotéine hémagglutinine du virus influenza (métabolisme)</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Lymphocytes B (immunologie)</term>
<term>Réactions croisées</term>
<term>Tests d'inhibition de l'hémagglutination</term>
<term>Tests de neutralisation</term>
<term>Virus de la grippe A (immunologie)</term>
<term>Épitopes (immunologie)</term>
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<term>Anticorps neutralisants</term>
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<term>Hemagglutination Inhibition Tests</term>
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<div type="abstract" xml:lang="en">Influenza A viruses are classified into 16 subtypes according to the serotypes of hemagglutinin (HA). It is generally thought that neutralizing antibodies (Abs) are not broadly cross-reactive among HA subtypes. We examined the repertoire of neutralizing Abs against influenza viruses in humans. B lymphocytes were collected from donors by apheresis, and Ab libraries were constructed by using phage-display technology. Anti-HA clones were isolated by screening with H3N2 viruses. Their binding activity was examined, and four kinds of Abs showing broad strain specificity were identified from one donor. Two of the Abs, F045-092 and F026-427, were extensively analyzed. They neutralized not only H3N2 but also H1N1, H2N2, and H5N1 viruses, although the activities were largely varied. Flow cytometry suggested that they have the ability to bind to HA and HA1 artificially expressed on the cell surface. They show hemagglutination inhibition activity and do not compete with C179, an Ab thought to bind to the stalk region. F045-092 competes with Abs that recognize sites A and B for binding to HA. Furthermore, the serine at residue 136 in site A could be a part of the epitope. Thus, it is likely that F045-092 and F026-427 bind to a conserved epitope in the head region formed by HA1. Interestingly, while the V
<sub>H</sub>
1-69 gene can encode MAbs against the HA stem that are group 1 specific, F045-092 and its relatives that recognize the head region also use V
<sub>H</sub>
1-69. The possible epitope recognized by these clones is discussed.</div>
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