Kevin WieheDavid EasterhoffKan LuoNathan I. NicelyTodd BradleyFrederick H. JaegerS. Moses DennisonRuijun ZhangKrissey E. LloydChristina StolarchukRobert ParksLaura L. SutherlandRichard M. ScearceLynn MorrisJaranit KaewkungwalSorachai NitayaphanPunnee PitisuttithumSupachai Rerks-NgarmFaruk SinangilSanjay PhogatNelson L. MichaelJerome H. KimGarnett KelsoeDavid C. MontefioriGeorgia D. TomarasMattia BonsignoriSampa SantraThomas B. KeplerS. Munir AlamM. Anthony MoodyHua Xin LiaoBarton F. HaynesDuke University School of MedicineCentre for the AIDS Programme of Research in South AfricaMahidol UniversityArmed Forces Research Institute of Medical Sciences, ThailandThailand Ministry of Public HealthSanofi Pasteur Inc.Global Solutions for Infectious DiseasesWalter Reed Army Institute of ResearchHarvard UniversityBoston University2018-11-092018-11-092014-01-01Immunity. Vol.41, No.6 (2014), 909-91810974180107476132-s2.0-84918548024https://repository.li.mahidol.ac.th/handle/20.500.14594/34111© 2014 Elsevier Inc. 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.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.1016/j.immuni.2014.11.014