Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved
In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second variable (V2) region involving lysine (K) 169...
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| Vydáno v: | Immunity (Cambridge, Mass.) Ročník 41; číslo 6; s. 909 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
18.12.2014
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| ISSN: | 1097-4180, 1097-4180 |
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| Abstract | In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second variable (V2) region involving lysine (K) 169, the site of immune pressure in the RV144 vaccine efficacy trial. We found that humans and rhesus macaques used orthologous lambda variable gene segments encoding a glutamic acid-aspartic acid (ED) motif for K169 recognition. Structure determination of an unmutated ancestor antibody demonstrated that the V2 binding site was preconfigured for ED motif-mediated recognition prior to maturation. Thus, light chain usage for recognition of the site of immune pressure in the RV144 trial is highly conserved across species. These data indicate that the HIV-1 K169-recognizing ED motif has persisted over the diversification between rhesus macaques and humans, suggesting an evolutionary advantage of this antibody recognition mode. |
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| AbstractList | In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second variable (V2) region involving lysine (K) 169, the site of immune pressure in the RV144 vaccine efficacy trial. We found that humans and rhesus macaques used orthologous lambda variable gene segments encoding a glutamic acid-aspartic acid (ED) motif for K169 recognition. Structure determination of an unmutated ancestor antibody demonstrated that the V2 binding site was preconfigured for ED motif-mediated recognition prior to maturation. Thus, light chain usage for recognition of the site of immune pressure in the RV144 trial is highly conserved across species. These data indicate that the HIV-1 K169-recognizing ED motif has persisted over the diversification between rhesus macaques and humans, suggesting an evolutionary advantage of this antibody recognition mode. In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second variable (V2) region involving lysine (K) 169, the site of immune pressure in the RV144 vaccine efficacy trial. We found that humans and rhesus macaques used orthologous lambda variable gene segments encoding a glutamic acid-aspartic acid (ED) motif for K169 recognition. Structure determination of an unmutated ancestor antibody demonstrated that the V2 binding site was preconfigured for ED motif-mediated recognition prior to maturation. Thus, light chain usage for recognition of the site of immune pressure in the RV144 trial is highly conserved across species. These data indicate that the HIV-1 K169-recognizing ED motif has persisted over the diversification between rhesus macaques and humans, suggesting an evolutionary advantage of this antibody recognition mode.In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second variable (V2) region involving lysine (K) 169, the site of immune pressure in the RV144 vaccine efficacy trial. We found that humans and rhesus macaques used orthologous lambda variable gene segments encoding a glutamic acid-aspartic acid (ED) motif for K169 recognition. Structure determination of an unmutated ancestor antibody demonstrated that the V2 binding site was preconfigured for ED motif-mediated recognition prior to maturation. Thus, light chain usage for recognition of the site of immune pressure in the RV144 trial is highly conserved across species. These data indicate that the HIV-1 K169-recognizing ED motif has persisted over the diversification between rhesus macaques and humans, suggesting an evolutionary advantage of this antibody recognition mode. |
| Author | Parks, Robert Nitayaphan, Sorachai Haynes, Barton F Morris, Lynn Kelsoe, Garnett Scearce, Richard M Nicely, Nathan I Rerks-Ngarm, Supachai Zhang, Ruijun Moody, M Anthony Liao, Hua-Xin Kaewkungwal, Jaranit Kepler, Thomas B Luo, Kan Pitisuttithum, Punnee Dennison, S Moses Sutherland, Laura L Kim, Jerome H Phogat, Sanjay Bonsignori, Mattia Michael, Nelson L Easterhoff, David Lloyd, Krissey E Jaeger, Frederick H Santra, Sampa Alam, S Munir Tomaras, Georgia D Wiehe, Kevin Sinangil, Faruk Montefiori, David C Bradley, Todd Stolarchuk, Christina |
| Author_xml | – sequence: 1 givenname: Kevin surname: Wiehe fullname: Wiehe, Kevin email: kevin.wiehe@dm.duke.edu organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: kevin.wiehe@dm.duke.edu – sequence: 2 givenname: David surname: Easterhoff fullname: Easterhoff, David organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 3 givenname: Kan surname: Luo fullname: Luo, Kan organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 4 givenname: Nathan I surname: Nicely fullname: Nicely, Nathan I organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 5 givenname: Todd surname: Bradley fullname: Bradley, Todd organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 6 givenname: Frederick H surname: Jaeger fullname: Jaeger, Frederick H organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 7 givenname: S Moses surname: Dennison fullname: Dennison, S Moses organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 8 givenname: Ruijun surname: Zhang fullname: Zhang, Ruijun organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 9 givenname: Krissey E surname: Lloyd fullname: Lloyd, Krissey E organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 10 givenname: Christina surname: Stolarchuk fullname: Stolarchuk, Christina organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 11 givenname: Robert surname: Parks fullname: Parks, Robert organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 12 givenname: Laura L surname: Sutherland fullname: Sutherland, Laura L organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 13 givenname: Richard M surname: Scearce fullname: Scearce, Richard M organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 14 givenname: Lynn surname: Morris fullname: Morris, Lynn organization: National Institute for Communicable Diseases, Johannesburg 2131, SA and the Centre for the AIDS Programme of Research in South Africa (CAPRISA) – sequence: 15 givenname: Jaranit surname: Kaewkungwal fullname: Kaewkungwal, Jaranit organization: Department of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand – sequence: 16 givenname: Sorachai surname: Nitayaphan fullname: Nitayaphan, Sorachai organization: Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok 10400, Thailand – sequence: 17 givenname: Punnee surname: Pitisuttithum fullname: Pitisuttithum, Punnee organization: Department of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand – sequence: 18 givenname: Supachai surname: Rerks-Ngarm fullname: Rerks-Ngarm, Supachai organization: Department of Disease Control, Ministry of Public Health, Nonthaburi 11000, Thailand – sequence: 19 givenname: Faruk surname: Sinangil fullname: Sinangil, Faruk organization: Sanofi Pasteur, Inc., Swiftwater, PA 18370, USA – sequence: 20 givenname: Sanjay surname: Phogat fullname: Phogat, Sanjay organization: Global Solutions for Infectious Diseases, South San Francisco, CA 94080, USA – sequence: 21 givenname: Nelson L surname: Michael fullname: Michael, Nelson L organization: US Military Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA – sequence: 22 givenname: Jerome H surname: Kim fullname: Kim, Jerome H organization: US Military Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA – sequence: 23 givenname: Garnett surname: Kelsoe fullname: Kelsoe, Garnett organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 24 givenname: David C surname: Montefiori fullname: Montefiori, David C organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 25 givenname: Georgia D surname: Tomaras fullname: Tomaras, Georgia D organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 26 givenname: Mattia surname: Bonsignori fullname: Bonsignori, Mattia organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 27 givenname: Sampa surname: Santra fullname: Santra, Sampa organization: Beth Israel Deaconess Medical Center, Harvard University School of Medicine, Boston, MA 02215, USA – sequence: 28 givenname: Thomas B surname: Kepler fullname: Kepler, Thomas B organization: Department of Microbiology, Boston University, Boston, MA 02118, USA – sequence: 29 givenname: S Munir surname: Alam fullname: Alam, S Munir organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 30 givenname: M Anthony surname: Moody fullname: Moody, M Anthony organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 31 givenname: Hua-Xin surname: Liao fullname: Liao, Hua-Xin organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA – sequence: 32 givenname: Barton F surname: Haynes fullname: Haynes, Barton F email: barton.haynes@dm.duke.edu organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: barton.haynes@dm.duke.edu |
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| SubjectTerms | AIDS Vaccines Amino Acid Sequence Animals Antibodies, Viral - metabolism Antibody Affinity - genetics B-Lymphocytes - immunology Cells, Cultured Clinical Trials as Topic Conserved Sequence - genetics Epitope Mapping Epitopes, B-Lymphocyte - genetics Epitopes, B-Lymphocyte - immunology Epitopes, B-Lymphocyte - metabolism HIV Envelope Protein gp120 - genetics HIV Envelope Protein gp120 - immunology HIV Envelope Protein gp120 - metabolism HIV Infections - immunology HIV Infections - prevention & control HIV-1 - immunology Humans Immunoglobulin Light Chains - metabolism Macaca mulatta Molecular Sequence Data Mutation - genetics Phylogeny Protein Binding - genetics Protein Engineering |
| Title | Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved |
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