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Immunity. 2014 Dec 18;41(6):909-18. doi: 10.1016/j.immuni.2014.11.014. Epub 2014 Nov 29.

Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved.

Author information

1
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: kevin.wiehe@dm.duke.edu.
2
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
3
National Institute for Communicable Diseases, Johannesburg 2131, SA and the Centre for the AIDS Programme of Research in South Africa (CAPRISA).
4
Department of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
5
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok 10400, Thailand.
6
Department of Disease Control, Ministry of Public Health, Nonthaburi 11000, Thailand.
7
Sanofi Pasteur, Inc., Swiftwater, PA 18370, USA.
8
Global Solutions for Infectious Diseases, South San Francisco, CA 94080, USA.
9
US Military Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
10
Beth Israel Deaconess Medical Center, Harvard University School of Medicine, Boston, MA 02215, USA.
11
Department of Microbiology, Boston University, Boston, MA 02118, USA.
12
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: barton.haynes@dm.duke.edu.

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.

PMID:
25526306
PMCID:
PMC4324565
DOI:
10.1016/j.immuni.2014.11.014
[Indexed for MEDLINE]
Free PMC Article

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