| Literature DB >> 25526306 |
Kevin Wiehe1, David Easterhoff2, Kan Luo2, Nathan I Nicely2, Todd Bradley2, Frederick H Jaeger2, S Moses Dennison2, Ruijun Zhang2, Krissey E Lloyd2, Christina Stolarchuk2, Robert Parks2, Laura L Sutherland2, Richard M Scearce2, Lynn Morris3, Jaranit Kaewkungwal4, Sorachai Nitayaphan5, Punnee Pitisuttithum4, Supachai Rerks-Ngarm6, Faruk Sinangil7, Sanjay Phogat8, Nelson L Michael9, Jerome H Kim9, Garnett Kelsoe2, David C Montefiori2, Georgia D Tomaras2, Mattia Bonsignori2, Sampa Santra10, Thomas B Kepler11, S Munir Alam2, M Anthony Moody2, Hua-Xin Liao2, Barton F Haynes12.
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.Entities:
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Year: 2014 PMID： 25526306 PMCID： PMC4324565 DOI： 10.1016/j.immuni.2014.11.014
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745