Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity
Human high-affinity antibodies to pathogens often recognize unrelated ligands. The molecular origin and the role of this polyreactivity are largely unknown. Here, we report that HIV-1 broadly neutralizing antibodies (bNAbs) are frequently polyreactive, cross-reacting with non-HIV-1 molecules, includ...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718306995 |
| _version_ | 1817977039162966016 |
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| author | Julie Prigent Annaëlle Jarossay Cyril Planchais Caroline Eden Jérémy Dufloo Ayrin Kök Valérie Lorin Oxana Vratskikh Thérèse Couderc Timothée Bruel Olivier Schwartz Michael S. Seaman Oliver Ohlenschläger Jordan D. Dimitrov Hugo Mouquet |
| author_facet | Julie Prigent Annaëlle Jarossay Cyril Planchais Caroline Eden Jérémy Dufloo Ayrin Kök Valérie Lorin Oxana Vratskikh Thérèse Couderc Timothée Bruel Olivier Schwartz Michael S. Seaman Oliver Ohlenschläger Jordan D. Dimitrov Hugo Mouquet |
| author_sort | Julie Prigent |
| collection | DOAJ |
| description | Human high-affinity antibodies to pathogens often recognize unrelated ligands. The molecular origin and the role of this polyreactivity are largely unknown. Here, we report that HIV-1 broadly neutralizing antibodies (bNAbs) are frequently polyreactive, cross-reacting with non-HIV-1 molecules, including self-antigens. Mutating bNAb genes to increase HIV-1 binding and neutralization also results in de novo polyreactivity. Unliganded paratopes of polyreactive bNAbs with improved HIV-1 neutralization exhibit a conformational flexibility, which contributes to enhanced affinity of bNAbs to various HIV-1 envelope glycoproteins and non-HIV antigens. Binding adaptation of polyreactive bNAbs to the divergent ligands mainly involves hydrophophic interactions. Plasticity of bNAbs’ paratopes may, therefore, facilitate accommodating divergent viral variants, but it simultaneously triggers promiscuous binding to non-HIV-1 antigens. Thus, a certain level of polyreactivity can be a mark of adaptable antibodies displaying optimal pathogens’ recognition. |
| first_indexed | 2024-04-13T22:10:55Z |
| format | Article |
| id | doaj.art-94e93b8b4c694f2ab52f103c8961f5f0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T22:10:55Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-94e93b8b4c694f2ab52f103c8961f5f02022-12-22T02:27:44ZengElsevierCell Reports2211-12472018-05-012392568258110.1016/j.celrep.2018.04.101Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers PolyreactivityJulie Prigent0Annaëlle Jarossay1Cyril Planchais2Caroline Eden3Jérémy Dufloo4Ayrin Kök5Valérie Lorin6Oxana Vratskikh7Thérèse Couderc8Timothée Bruel9Olivier Schwartz10Michael S. Seaman11Oliver Ohlenschläger12Jordan D. Dimitrov13Hugo Mouquet14Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75015, FranceSorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, Paris 75006, FranceLaboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75015, FranceLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USAVirus & Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, FranceLaboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75015, FranceLaboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75015, FranceLaboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75015, FranceBiology of Infection Unit, INSERM U1117, Department of Cell Biology and Infection, Institut Pasteur, Paris 75015, FranceVirus & Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, FranceVirus & Immunity Unit, Department of Virology, Institut Pasteur, Paris 75015, FranceBeth Israel Deaconess Medical Center, Boston, MA 02215, USALeibniz Institute on Aging - Fritz Lipmann Institute, Jena 07745, GermanySorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, Paris 75006, FranceLaboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris 75015, FranceHuman high-affinity antibodies to pathogens often recognize unrelated ligands. The molecular origin and the role of this polyreactivity are largely unknown. Here, we report that HIV-1 broadly neutralizing antibodies (bNAbs) are frequently polyreactive, cross-reacting with non-HIV-1 molecules, including self-antigens. Mutating bNAb genes to increase HIV-1 binding and neutralization also results in de novo polyreactivity. Unliganded paratopes of polyreactive bNAbs with improved HIV-1 neutralization exhibit a conformational flexibility, which contributes to enhanced affinity of bNAbs to various HIV-1 envelope glycoproteins and non-HIV antigens. Binding adaptation of polyreactive bNAbs to the divergent ligands mainly involves hydrophophic interactions. Plasticity of bNAbs’ paratopes may, therefore, facilitate accommodating divergent viral variants, but it simultaneously triggers promiscuous binding to non-HIV-1 antigens. Thus, a certain level of polyreactivity can be a mark of adaptable antibodies displaying optimal pathogens’ recognition.http://www.sciencedirect.com/science/article/pii/S2211124718306995antibodyB cellsHIV-1polyreactivityautoreactivity |
| spellingShingle | Julie Prigent Annaëlle Jarossay Cyril Planchais Caroline Eden Jérémy Dufloo Ayrin Kök Valérie Lorin Oxana Vratskikh Thérèse Couderc Timothée Bruel Olivier Schwartz Michael S. Seaman Oliver Ohlenschläger Jordan D. Dimitrov Hugo Mouquet Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity Cell Reports antibody B cells HIV-1 polyreactivity autoreactivity |
| title | Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity |
| title_full | Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity |
| title_fullStr | Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity |
| title_full_unstemmed | Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity |
| title_short | Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity |
| title_sort | conformational plasticity in broadly neutralizing hiv 1 antibodies triggers polyreactivity |
| topic | antibody B cells HIV-1 polyreactivity autoreactivity |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718306995 |
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