Document Detail


Identification and characterization of a neutralization site within the second variable region of human immunodeficiency virus type 1 gp120.
MedLine Citation:
PMID:  1370558     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Two monoclonal antibodies designated BAT085 and G3-136 were raised by immunizing BALB/c mice with gp120 purified from human immunodeficiency virus type 1 (HIV-1) IIIB-infected H9 cell extracts. Among three HIV-1 laboratory isolates (IIIB, MN, and RF), BAT085 neutralized only IIIB infection of CEM-SS cells, whereas G3-136 neutralized both IIIB and RF. These antibodies also neutralized a few primary HIV-1 isolates in the infection of activated human peripheral blood mononuclear cells. In indirect immunofluorescence assays, BAT085 bound to H9 cells infected with IIIB or MN, while G3-136 bound to H9 cells infected with IIIB or RF, but not MN. Using sequence-overlapping synthetic peptides of HIV-1 IIIB gp120, the binding site of BAT085 and G3-136 was mapped to a peptidic segment in the V2 region (amino acid residues 169 to 183). The binding of these antibodies to immobilized gp120 was not inhibited by the antibodies directed to the principal neutralization determinant in the V3 region or to the CD4-binding domain of gp120. In a competition enzyme-linked immunosorbent assay, soluble CD4 inhibited G3-136 but not BAT085 from binding to gp120. Deglycosylation of gp120 by endo-beta-N-acetylglucosaminidase H or reduction of gp120 by dithiothreitol diminished its reactivity with G3-136 but not with BAT085. These results indicate that the V2 region of gp120 contains multiple neutralization determinants recognized by antibodies in both a conformation-dependent and -independent manner.
Authors:
M S Fung; C R Sun; W L Gordon; R S Liou; T W Chang; W N Sun; E S Daar; D D Ho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  66     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  1992 Feb 
Date Detail:
Created Date:  1992-02-14     Completed Date:  1992-02-14     Revised Date:  2010-09-07    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  848-56     Citation Subset:  IM; X    
Affiliation:
Tanox Biosystems, Inc., Houston, Texas 77025.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Antibodies, Monoclonal*
Binding Sites, Antibody*
Binding, Competitive
Cell Line
Enzyme-Linked Immunosorbent Assay
Epitopes / analysis,  immunology
Genetic Variation
HIV Envelope Protein gp120 / analysis,  genetics,  immunology*
HIV-1 / genetics,  immunology*,  isolation & purification
Humans
Kinetics
Models, Structural
Molecular Sequence Data
Neutralization Tests
Peptides / chemical synthesis,  immunology
Protein Conformation
Grant Support
ID/Acronym/Agency:
AI25541/AI/NIAID NIH HHS; AI27742/AI/NIAID NIH HHS; AI28747/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Binding Sites, Antibody; 0/Epitopes; 0/HIV Envelope Protein gp120; 0/Peptides
Comments/Corrections

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