skip to main content

Title: Antibody Light-Chain-Restricted Recognition of the Site of Immune Pressure in the RV144 HIV-1 Vaccine Trial Is Phylogenetically Conserved

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. In conclusion, 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.
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [3] ;  [5] ;  [6] ;  [7] more »;  [8] ;  [8] ;  [1] ;  [1] ;  [1] ;  [1] ;  [9] ;  [10] ;  [1] ;  [1] ;  [1] ;  [1] « less
  1. Duke Univ., Durham, NC (United States). School of Medicine, Human Vaccine Inst.
  2. National Inst. for Communicable Diseases, Johannesburg (South Africa). Centre for the AIDS Programme of Research in South Africa (CAPRISA)
  3. Mahidol Univ., Bangkok (Thailand). Dept. of Tropical Medicine
  4. Armed Forces Research Inst. of Medical Sciences (AFRIMS), Bangkok (Thailand)
  5. Ministry of Public Health, Nonthaburi (Thailand). Dept. of Disease Control
  6. Sanofi Pasteur, Inc., Swiftwater, PA (United States)
  7. Global Solutions for Infectious Diseases, South San Francisco, CA (United States)
  8. Walter Reed Army Inst. of Research, Silver Spring, MD (United States)
  9. Harvard Univ., Cambridge, MA (United States). School of Medicine, Beth Israel Deaconess Medical Center
  10. Boston Univ., MA (United States). Dept. of Microbiology
Publication Date:
OSTI Identifier:
1233905
Grant/Contract Number:
W-31-109-Eng-38; P30-AI-64518; 5T32-AI007392; OPP1033098; UMI-AI100645
Type:
Published Article
Journal Name:
Immunity
Additional Journal Information:
Journal Volume: 41; Journal Issue: 6; Journal ID: ISSN 1074-7613
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); Bill & Melinda Gates Foundation; National Institutes of Health (NIH)
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES