TY - JOUR
T1 - Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved
AU - Wiehe, Kevin
AU - Easterhoff, David
AU - Luo, Kan
AU - Nicely, Nathan I.
AU - Bradley, Todd
AU - Jaeger, Frederick H.
AU - Dennison, S. Moses
AU - Zhang, Ruijun
AU - Lloyd, Krissey E.
AU - Stolarchuk, Christina
AU - Parks, Robert
AU - Sutherland, Laura L.
AU - Scearce, Richard M.
AU - Morris, Lynn
AU - Kaewkungwal, Jaranit
AU - Nitayaphan, Sorachai
AU - Pitisuttithum, Punnee
AU - Rerks-Ngarm, Supachai
AU - Sinangil, Faruk
AU - Phogat, Sanjay
AU - Michael, Nelson L.
AU - Kim, Jerome H.
AU - Kelsoe, Garnett
AU - Montefiori, David C.
AU - Tomaras, Georgia D.
AU - Bonsignori, Mattia
AU - Santra, Sampa
AU - Kepler, Thomas B.
AU - Alam, S. Munir
AU - Moody, M. Anthony
AU - Liao, Hua Xin
AU - Haynes, Barton F.
N1 - Funding Information:
This work was supported by Collaboration for AIDS Vaccine Discovery grants from the Bill & Melinda Gates Foundation (grant ID OPP1033098 ) and by the Center for HIV/AIDS Vaccine Immunology-Immuongen Discovery (CHAVI-ID; UMI-AI100645 ) grant from NIH/NIAID/DAIDS . This work was also supported by grant number 5T32-AI007392 from the NIAID (NIH) . Flow cytometry work was additionally supported by The Duke University Center for AIDS Research Flow Cytometry core (NIAID, NIH, CFAR grant P30-AI-64518 ). Funding was also provided by Interagency Agreement Y1-AI-2642-12 between U.S. Army Medical Research and Material Command (USAMRMC) and the National Institute of Allergy and Infectious Diseases through a cooperative agreement ( W81XWH-07-2-0067 ) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. , and the U.S. Department of Defense (DOD) . The views expressed in this article are those of the authors and should not be construed as official or as representing the views of the Department of Defense or the Department of the Army. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences , under Contract No. W-31-109-Eng-38 . We thank A. Foulger for expert technical assistance in antibody production; D. Marshall and J. Whitesides for expert technical assistance in flow cytometry; A. Martelli for expert technical assistance in neutralization assays; and K. Soderberg and S. Bowen for project management.
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/12/18
Y1 - 2014/12/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84918548024&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2014.11.014
DO - 10.1016/j.immuni.2014.11.014
M3 - Article
C2 - 25526306
AN - SCOPUS:84918548024
SN - 1074-7613
VL - 41
SP - 909
EP - 918
JO - Immunity
JF - Immunity
IS - 6
ER -