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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Published in:Immunity (Cambridge, Mass.) Vol. 41; no. 6; p. 909
Main Authors: 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
Language:English
Published: United States 18.12.2014
Subjects:
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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Summary: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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ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2014.11.014