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Title: Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved
Authors: Kevin Wiehe
David Easterhoff
Kan Luo
Nathan I. Nicely
Todd Bradley
Frederick H. Jaeger
S. Moses Dennison
Ruijun Zhang
Krissey E. Lloyd
Christina Stolarchuk
Robert Parks
Laura L. Sutherland
Richard M. Scearce
Lynn Morris
Jaranit Kaewkungwal
Sorachai Nitayaphan
Punnee Pitisuttithum
Supachai Rerks-Ngarm
Faruk Sinangil
Sanjay Phogat
Nelson L. Michael
Jerome H. Kim
Garnett Kelsoe
David C. Montefiori
Georgia D. Tomaras
Mattia Bonsignori
Sampa Santra
Thomas B. Kepler
S. Munir Alam
M. Anthony Moody
Hua Xin Liao
Barton F. Haynes
Duke University School of Medicine
Centre for the AIDS Programme of Research in South Africa
Mahidol University
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Sanofi Pasteur Inc.
Global Solutions for Infectious Diseases
Walter Reed Army Institute of Research
Harvard University
Boston University
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Jan-2014
Citation: Immunity. Vol.41, No.6 (2014), 909-918
Abstract: © 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.
ISSN: 10974180
Appears in Collections:Scopus 2011-2015

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