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Title: Structural analysis of a novel rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region critical for receptor and co-receptor binding

Journal Article · · Emerging Microbes & Infections
DOI:https://doi.org/10.1038/emi.2015.44· OSTI ID:1214782
 [1];  [2];  [2];  [2];  [2];  [2];  [1]
  1. New York Univ. School of Medicine, New York, NY (United States)
  2. Univ. of Massachusetts Medical School, Worcester, MA (United States)
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The fourth conserved region (C4) in the HIV-1 envelope glycoprotein (Env) gp120 is a structural element that is important for its function, as it binds to both the receptor CD4 and the co-receptor CCR5/CXCR4. It has long been known that this region is highly immunogenic and that it harbors B-cell as well as T-cell epitopes. It is the target of a number of antibodies in animal studies, which are called CD4-blockers. However, the mechanism by which the virus shields itself from such antibody responses is not known. Here, we determined the crystal structure of R53 in complex with its epitope peptide using a novel anti-C4 rabbit monoclonal antibody R53. Our data show that although the epitope of R53 covers a highly conserved sequence 433AMYAPPI439, it is not available in the gp120 trimer and in the CD4-bound conformation. Our results suggest a masking mechanism to explain how HIV-1 protects this critical region from the human immune system.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States); Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-06CH11357; AC02-98CH10886
OSTI ID:
1214782
Journal Information:
Emerging Microbes & Infections, Vol. 4, Issue 7; ISSN 2222-1751
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 12 works
Citation information provided by
Web of Science

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Cited By (4)

From rabbit antibody repertoires to rabbit monoclonal antibodies journal March 2017
Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines journal September 2017
Immunoregulatory functions of immune complexes in vaccine and therapy journal August 2016
DNA immunization as a technology platform for monoclonal antibody induction journal January 2016

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
C4
CD4
Env
HIV-1
monoclonal antibody