Cross-neutralization of influenza A viruses mediated by a single antibody loop
Identifieur interne : 000B30 ( Main/Exploration ); précédent : 000B29; suivant : 000B31Cross-neutralization of influenza A viruses mediated by a single antibody loop
Auteurs : Damian C. Ekiert [États-Unis] ; Arun K. Kashyap [États-Unis] ; John Steel [États-Unis] ; Adam Rubrum [États-Unis] ; Gira Bhabha [États-Unis] ; Reza Khayat [États-Unis] ; Jeong Hyun Lee [États-Unis] ; Michael A. Dillon [États-Unis] ; Ryann E. O Eil [États-Unis] ; Aleksandr M. Faynboym [États-Unis] ; Michael Horowitz [États-Unis] ; Lawrence Horowitz [États-Unis] ; Andrew B. Ward [États-Unis] ; Peter Palese [États-Unis] ; Richard Webby [États-Unis] ; Richard A. Lerner [États-Unis] ; Ramesh R. Bhatt [États-Unis] ; Ian A. Wilson [États-Unis]Source :
- Nature [ 0028-0836 ] ; 2012-09-27.
Abstract
Immune recognition of protein antigens relies on the combined interaction of multiple antibody loops, which provide a fairly large footprint and constrain the size and shape of protein surfaces that can be targeted. Single protein loops can mediate extremely high-affinity binding, but it is unclear whether such a mechanism is available to antibodies. Here we report the isolation and characterization of an antibody called C05, which neutralizes strains from multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and electron microscopy structures show that C05 recognizes conserved elements of the receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of the haemagglutinin receptor-binding site is dominated by a single heavy-chain complementarity-determining region 3 loop, with minor contacts from heavy-chain complementarity-determining region 1, and is sufficient to achieve nanomolar binding with a minimal footprint. Thus, binding predominantly with a single loop can allow antibodies to target small, conserved functional sites on otherwise hypervariable antigens.
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DOI: 10.1038/nature11414
Affiliations:
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Ward</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037</wicri:regionArea><wicri:noRegion>California 92037</wicri:noRegion></affiliation></author><author><name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, New York 10029-6574</wicri:regionArea><wicri:noRegion>New York 10029-6574</wicri:noRegion></affiliation></author><author><name sortKey="Webby, Richard" sort="Webby, Richard" uniqKey="Webby R" first="Richard" last="Webby">Richard Webby</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Infectious Diseases, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105</wicri:regionArea><wicri:noRegion>Tennessee 38105</wicri:noRegion></affiliation></author><author><name sortKey="Lerner, Richard A" sort="Lerner, Richard A" uniqKey="Lerner R" first="Richard A." last="Lerner">Richard A. Lerner</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037</wicri:regionArea><wicri:noRegion>California 92037</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037</wicri:regionArea><wicri:noRegion>California 92037</wicri:noRegion></affiliation></author><author><name sortKey="Bhatt, Ramesh R" sort="Bhatt, Ramesh R" uniqKey="Bhatt R" first="Ramesh R." last="Bhatt">Ramesh R. Bhatt</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Sea Lane Biotechnologies, 2450 Bayshore Parkway, Mountain View, California 94043</wicri:regionArea><wicri:noRegion>California 94043</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037</wicri:regionArea><wicri:noRegion>California 92037</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037</wicri:regionArea><wicri:noRegion>California 92037</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Nature</title><idno type="ISSN">0028-0836</idno><idno type="eISSN">1476-4687</idno><imprint><publisher>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</publisher><date when="2012-09-27">2012-09-27</date><biblScope unit="vol">489</biblScope><biblScope unit="issue">7417</biblScope><biblScope unit="page" from="526">526</biblScope><biblScope unit="page" to="532">532</biblScope><date type="Copyright" when="2012">2012</date></imprint><idno type="ISSN">0028-0836</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0028-0836</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="eng">Immune recognition of protein antigens relies on the combined interaction of multiple antibody loops, which provide a fairly large footprint and constrain the size and shape of protein surfaces that can be targeted. Single protein loops can mediate extremely high-affinity binding, but it is unclear whether such a mechanism is available to antibodies. Here we report the isolation and characterization of an antibody called C05, which neutralizes strains from multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and electron microscopy structures show that C05 recognizes conserved elements of the receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of the haemagglutinin receptor-binding site is dominated by a single heavy-chain complementarity-determining region 3 loop, with minor contacts from heavy-chain complementarity-determining region 1, and is sufficient to achieve nanomolar binding with a minimal footprint. Thus, binding predominantly with a single loop can allow antibodies to target small, conserved functional sites on otherwise hypervariable antigens.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Ekiert, Damian C" sort="Ekiert, Damian C" uniqKey="Ekiert D" first="Damian C." last="Ekiert">Damian C. Ekiert</name></noRegion><name sortKey="Bhabha, Gira" sort="Bhabha, Gira" uniqKey="Bhabha G" first="Gira" last="Bhabha">Gira Bhabha</name><name sortKey="Bhatt, Ramesh R" sort="Bhatt, Ramesh R" uniqKey="Bhatt R" first="Ramesh R." last="Bhatt">Ramesh R. Bhatt</name><name sortKey="Dillon, Michael A" sort="Dillon, Michael A" uniqKey="Dillon M" first="Michael A." last="Dillon">Michael A. Dillon</name><name sortKey="Faynboym, Aleksandr M" sort="Faynboym, Aleksandr M" uniqKey="Faynboym A" first="Aleksandr M." last="Faynboym">Aleksandr M. Faynboym</name><name sortKey="Horowitz, Lawrence" sort="Horowitz, Lawrence" uniqKey="Horowitz L" first="Lawrence" last="Horowitz">Lawrence Horowitz</name><name sortKey="Horowitz, Michael" sort="Horowitz, Michael" uniqKey="Horowitz M" first="Michael" last="Horowitz">Michael Horowitz</name><name sortKey="Kashyap, Arun K" sort="Kashyap, Arun K" uniqKey="Kashyap A" first="Arun K." last="Kashyap">Arun K. Kashyap</name><name sortKey="Khayat, Reza" sort="Khayat, Reza" uniqKey="Khayat R" first="Reza" last="Khayat">Reza Khayat</name><name sortKey="Lee, Jeong Hyun" sort="Lee, Jeong Hyun" uniqKey="Lee J" first="Jeong Hyun" last="Lee">Jeong Hyun Lee</name><name sortKey="Lerner, Richard A" sort="Lerner, Richard A" uniqKey="Lerner R" first="Richard A." last="Lerner">Richard A. Lerner</name><name sortKey="Lerner, Richard A" sort="Lerner, Richard A" uniqKey="Lerner R" first="Richard A." last="Lerner">Richard A. Lerner</name><name sortKey="O Eil, Ryann E" sort="O Eil, Ryann E" uniqKey="O Eil R" first="Ryann E." last="O Eil">Ryann E. O Eil</name><name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name><name sortKey="Rubrum, Adam" sort="Rubrum, Adam" uniqKey="Rubrum A" first="Adam" last="Rubrum">Adam Rubrum</name><name sortKey="Steel, John" sort="Steel, John" uniqKey="Steel J" first="John" last="Steel">John Steel</name><name sortKey="Ward, Andrew B" sort="Ward, Andrew B" uniqKey="Ward A" first="Andrew B." last="Ward">Andrew B. Ward</name><name sortKey="Webby, Richard" sort="Webby, Richard" uniqKey="Webby R" first="Richard" last="Webby">Richard Webby</name><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name><name sortKey="Wilson, Ian A" sort="Wilson, Ian A" uniqKey="Wilson I" first="Ian A." last="Wilson">Ian A. Wilson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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