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Convergent Evolution in Breadth of Two V(H)6-1-Encoded Influenza Antibody Clonotypes from a Single Donor
Understanding how broadly neutralizing antibodies (bnAbs) to influenza hemagglutinin (HA) naturally develop in humans is critical to the design of universal influenza vaccines. Several classes of bnAbs directed to the conserved HA stem were found in multiple individuals, including one encoded by hea...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486241/ https://www.ncbi.nlm.nih.gov/pubmed/32619441 http://dx.doi.org/10.1016/j.chom.2020.06.003 |
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author | Wu, Nicholas C. Andrews, Sarah F. Raab, Julie E. O’Connell, Sarah Schramm, Chaim A. Ding, Xintao Chambers, Michael J. Leung, Kwanyee Wang, Lingshu Zhang, Yi Mascola, John R. Douek, Daniel C. Ledgerwood, Julie E. McDermott, Adrian B. Wilson, Ian A. |
author_facet | Wu, Nicholas C. Andrews, Sarah F. Raab, Julie E. O’Connell, Sarah Schramm, Chaim A. Ding, Xintao Chambers, Michael J. Leung, Kwanyee Wang, Lingshu Zhang, Yi Mascola, John R. Douek, Daniel C. Ledgerwood, Julie E. McDermott, Adrian B. Wilson, Ian A. |
author_sort | Wu, Nicholas C. |
collection | PubMed |
description | Understanding how broadly neutralizing antibodies (bnAbs) to influenza hemagglutinin (HA) naturally develop in humans is critical to the design of universal influenza vaccines. Several classes of bnAbs directed to the conserved HA stem were found in multiple individuals, including one encoded by heavy-chain variable domain V(H)6-1. We describe two genetically similar V(H)6-1 bnAb clonotypes from the same individual that exhibit different developmental paths toward broad neutralization activity. One clonotype evolved from a germline precursor recognizing influenza group 1 subtypes to gain breadth to group 2 subtypes. The other clonotype recognized group 2 subtypes and developed binding to group 1 subtypes through somatic hypermutation. Crystal structures reveal that the specificity differences are primarily mediated by complementarity-determining region H3 (CDR H3). Thus, while V(H)6-1 provides a framework for development of HA stem-directed bnAbs, sequence differences in CDR H3 junctional regions during VDJ recombination can alter reactivity and evolutionary pathways toward increased breadth. |
format | Online Article Text |
id | pubmed-7486241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74862412020-09-24 Convergent Evolution in Breadth of Two V(H)6-1-Encoded Influenza Antibody Clonotypes from a Single Donor Wu, Nicholas C. Andrews, Sarah F. Raab, Julie E. O’Connell, Sarah Schramm, Chaim A. Ding, Xintao Chambers, Michael J. Leung, Kwanyee Wang, Lingshu Zhang, Yi Mascola, John R. Douek, Daniel C. Ledgerwood, Julie E. McDermott, Adrian B. Wilson, Ian A. Cell Host Microbe Article Understanding how broadly neutralizing antibodies (bnAbs) to influenza hemagglutinin (HA) naturally develop in humans is critical to the design of universal influenza vaccines. Several classes of bnAbs directed to the conserved HA stem were found in multiple individuals, including one encoded by heavy-chain variable domain V(H)6-1. We describe two genetically similar V(H)6-1 bnAb clonotypes from the same individual that exhibit different developmental paths toward broad neutralization activity. One clonotype evolved from a germline precursor recognizing influenza group 1 subtypes to gain breadth to group 2 subtypes. The other clonotype recognized group 2 subtypes and developed binding to group 1 subtypes through somatic hypermutation. Crystal structures reveal that the specificity differences are primarily mediated by complementarity-determining region H3 (CDR H3). Thus, while V(H)6-1 provides a framework for development of HA stem-directed bnAbs, sequence differences in CDR H3 junctional regions during VDJ recombination can alter reactivity and evolutionary pathways toward increased breadth. Cell Press 2020-09-09 /pmc/articles/PMC7486241/ /pubmed/32619441 http://dx.doi.org/10.1016/j.chom.2020.06.003 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wu, Nicholas C. Andrews, Sarah F. Raab, Julie E. O’Connell, Sarah Schramm, Chaim A. Ding, Xintao Chambers, Michael J. Leung, Kwanyee Wang, Lingshu Zhang, Yi Mascola, John R. Douek, Daniel C. Ledgerwood, Julie E. McDermott, Adrian B. Wilson, Ian A. Convergent Evolution in Breadth of Two V(H)6-1-Encoded Influenza Antibody Clonotypes from a Single Donor |
title | Convergent Evolution in Breadth of Two V(H)6-1-Encoded Influenza Antibody Clonotypes from a Single Donor |
title_full | Convergent Evolution in Breadth of Two V(H)6-1-Encoded Influenza Antibody Clonotypes from a Single Donor |
title_fullStr | Convergent Evolution in Breadth of Two V(H)6-1-Encoded Influenza Antibody Clonotypes from a Single Donor |
title_full_unstemmed | Convergent Evolution in Breadth of Two V(H)6-1-Encoded Influenza Antibody Clonotypes from a Single Donor |
title_short | Convergent Evolution in Breadth of Two V(H)6-1-Encoded Influenza Antibody Clonotypes from a Single Donor |
title_sort | convergent evolution in breadth of two v(h)6-1-encoded influenza antibody clonotypes from a single donor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486241/ https://www.ncbi.nlm.nih.gov/pubmed/32619441 http://dx.doi.org/10.1016/j.chom.2020.06.003 |
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