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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Veröffentlicht in:	Immunity (Cambridge, Mass.) Jg. 41; H. 6; S. 909
Hauptverfasser:	Wiehe, Kevin, Easterhoff, David, Luo, Kan, Nicely, Nathan I, Bradley, Todd, Jaeger, Frederick H, Dennison, S Moses, Zhang, Ruijun, Lloyd, Krissey E, Stolarchuk, Christina, Parks, Robert, Sutherland, Laura L, Scearce, Richard M, Morris, Lynn, Kaewkungwal, Jaranit, Nitayaphan, Sorachai, Pitisuttithum, Punnee, Rerks-Ngarm, Supachai, Sinangil, Faruk, Phogat, Sanjay, Michael, Nelson L, Kim, Jerome H, Kelsoe, Garnett, Montefiori, David C, Tomaras, Georgia D, Bonsignori, Mattia, Santra, Sampa, Kepler, Thomas B, Alam, S Munir, Moody, M Anthony, Liao, Hua-Xin, Haynes, Barton F
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 18.12.2014
Schlagworte:	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
ISSN:	1097-4180, 1097-4180
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4180 1097-4180
DOI:	10.1016/j.immuni.2014.11.014