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PMID: 1637373 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Variant-specific monoclonal and group-specific polyclonal human immunodeficiency virus type 1 neutralizing antibodies raised with synthetic peptides from the gp120 third variable domain.

Journal of virology ·Vol. 66 ·No. 3 ·1992-03-00 ·Pages 1823-31

Laman JD, Schellekens MM, Abacioglu YH, Lewis GK, Tersmette M, Fouchier RA, Langedijk JP, Claassen E, Boersma WJ

Abstract

The third variable (V3) domain of the human immunodeficiency virus type 1 (HIV-1) external membrane glycoprotein gp120 is of crucial importance in eliciting neutralizing antibodies in infected persons. Polyclonal (PAb) and monoclonal (MAb) antibodies directed against selected epitopes in the V3 domain are valuable tools for analysis of the involvement of such sequences in neutralization and for definition of the relation between amino acid variability and immunological cross-reactions. The aim of this study was to obtain such site-specific antibodies. By using synthetic peptides derived from the V3 domain, a group-specific neutralizing PAb, two high-affinity HIV-1 IIIB neutralizing MAb, and two nonneutralizing MAb were raised. A 15-amino-acid peptide overlapping the tip of the V3 domain of HIV-1 MN was used to produce a rabbit PAb (W0/07). This PAb inhibited syncytium formation induced by HIV-1 IIIB and four field isolates. A similar IIIB-derived peptide was used to generate two murine immunoglobulin G1 (IgG1) MAb (IIIB-V3-13 and IIIB-V3-34). Pepscan analysis mapped the binding site of IIIB-V3-34 to the sequence IRIQRGPGR. The Kds of IIIB-V3-13 and IIIB-V3-34 for gp120 were 6.8 x 10(-11) and 1.6 x 10(-10) M, respectively. These MAb neutralized IIIB but not MN and inhibited syncytium formation induced by IIIB. They are applicable in enzyme-linked immunosorbent assays, immunocytochemistry, and flow cytometry. A peptide covering the left base of the V3 domain was used to generate two murine IgG1 MAb (IIIB-V3-21 and IIIB-V3-26). The binding site of IIIB-V3-21 was mapped to the sequence INCTRPN. These MAb did not neutralize HIV-1 and did not inhibit syncytium formation. This study supports the notion that HIV-1 neutralizing antibodies suitable for multiassay performance can be obtained with synthetic peptides and that high-affinity MAb can be generated. Such site-specific antibodies are useful reagents in the analysis of HIV-1 neutralization. In addition, the cross-neutralization of different viral strains by PAb generated through single-peptide immunization is directly relevant to vaccine development.

MeSH Terms
Amino Acid Sequence Antibodies, Monoclonal/immunology Antibody Specificity Cell Fusion Cells, Cultured HIV Antibodies/immunology HIV Antigens/immunology HIV Envelope Protein gp120/chemistry,immunology HIV-1/immunology Humans In Vitro Techniques Molecular Sequence Data Neutralization Tests Peptides/immunology
Chemicals
Antibodies, Monoclonal HIV Antibodies HIV Antigens HIV Envelope Protein gp120 Peptides
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Laman J D
Department of Immunology and Medical Microbiology, TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
Schellekens M M
Abacioglu Y H
Lewis G K
Tersmette M
Fouchier R A
Langedijk J P
Claassen E
Boersma W J
References (44)
44 references, click to expand
  1. The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: a possible function in viral fusion?
    AIDS Res Hum Retroviruses. 1991 Jan;7(1):3-16 PMID: 2015114
  2. Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus.
    Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):542-6 PMID: 1988952
  3. Dextran sulfate blocks antibody binding to the principal neutralizing domain of human immunodeficiency virus type 1 without interfering with gp120-CD4 interactions.
    J Virol. 1991 Mar;65(3):1543-50 PMID: 1995952
  4. Neutralizing cross-reactive and non-neutralizing monoclonal antibodies to HIV-1 gp120.
    AIDS. 1990 Oct;4(10):953-60 PMID: 1702001
  5. Synthetic peptide conjugates with horseradish peroxidase and beta-galactosidase for use in epitope-specific immunocytochemistry and ELISA.
    J Immunol Methods. 1991 Dec 15;145(1-2):1-10 PMID: 1722493
  6. Immunocytochemical determination of antigen and epitope specificity of HIV-1-specific B cells in lymph-node biopsies from HIV-1-infected individuals.
    AIDS. 1991 Mar;5(3):255-62 PMID: 1711861
  7. Neutralization of HIV-1: a paradox of humoral proportions.
    FASEB J. 1991 Jul;5(10):2437-55 PMID: 1712328
  8. Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1.
    Science. 1990 Dec 14;250(4987):1590-3 PMID: 1703322
  9. HIV-1 neutralizing monoclonal antibodies induced by a synthetic peptide.
    AIDS Res Hum Retroviruses. 1990 Sep;6(9):1115-23 PMID: 1702301
  10. Epitope prediction and confirmation for the human androgen receptor: generation of monoclonal antibodies for multi-assay performance following the synthetic peptide strategy.
    Biochim Biophys Acta. 1991 Jan 23;1073(1):23-32 PMID: 1703791
  11. Human monoclonal antibody that recognizes the V3 region of human immunodeficiency virus gp120 and neutralizes the human T-lymphotropic virus type IIIMN strain.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8597-601 PMID: 1700435
  12. Neutralizing activity of anti-peptide antibodies against the principal neutralization domain of human immunodeficiency virus type 1.
    J Gen Virol. 1991 Oct;72 ( Pt 10):2519-26 PMID: 1919529
  13. Fixation of cryo-sections under HIV-1 inactivating conditions: integrity of antigen binding sites and cell surface antigens.
    Histochemistry. 1991;96(2):177-83 PMID: 1917574
  14. LAV revisited: origins of the early HIV-1 isolates from Institut Pasteur.
    Science. 1991 May 17;252(5008):961-5 PMID: 2035026
  15. Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein.
    Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3238-42 PMID: 2014246
  16. Immunodominance and antigenic variation of the principal neutralization domain of HIV-1.
    Virology. 1991 Apr;181(2):481-9 PMID: 2014634
  17. Phenotypic heterogeneity in a panel of infectious molecular human immunodeficiency virus type 1 clones derived from a single individual.
    J Virol. 1991 Apr;65(4):1968-75 PMID: 2002552
  18. Identification of the principal neutralizing determinant of human immunodeficiency virus type 1 as a fusion domain.
    J Virol. 1991 Jan;65(1):190-4 PMID: 1985197
  19. Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV.
    Proc Natl Acad Sci U S A. 1988 Sep;85(18):6944-8 PMID: 3413127
  20. Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees.
    Proc Natl Acad Sci U S A. 1988 Jun;85(12):4478-82 PMID: 2454471
  21. Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120.
    Proc Natl Acad Sci U S A. 1988 May;85(9):3198-202 PMID: 2452447
  22. Specificity and function of the individual amino acids of an important determinant of human immunodeficiency virus type 1 that induces neutralizing activity.
    J Gen Virol. 1989 Jun;70 ( Pt 6):1505-12 PMID: 2471813
  23. Human immunodeficiency virus-infected T cells and monocytes are killed by monoclonal human anti-gp41 antibodies coupled to ricin A chain.
    Proc Natl Acad Sci U S A. 1989 Mar;86(6):1987-91 PMID: 2538826
  24. Interaction between the human T-cell lymphotropic virus type IIIB envelope glycoprotein gp120 and the surface antigen CD4: role of carbohydrate in binding and cell fusion.
    Proc Natl Acad Sci U S A. 1987 Aug;84(15):5424-8 PMID: 3037551
  25. Lysis of cells infected with HIV-1 by human lymphocytes targeted with monoclonal antibody heteroconjugates.
    J Immunol. 1988 Apr 15;140(8):2609-13 PMID: 2965725
  26. Interference with HIV-induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase.
    Nature. 1987 Nov 5-11;330(6143):74-7 PMID: 2959866
  27. Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex.
    J Virol. 1988 Jun;62(6):2026-32 PMID: 3130494
  28. Effects of anti-gp120 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1.
    J Virol. 1988 Oct;62(10):3695-702 PMID: 2458487
  29. Characteristics of a neutralizing monoclonal antibody to the HIV envelope glycoprotein.
    AIDS Res Hum Retroviruses. 1988 Jun;4(3):187-97 PMID: 2456088
  30. Neutralizing monoclonal antibodies to the AIDS virus.
    AIDS. 1988 Feb;2(1):25-9 PMID: 2451922
  31. Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope.
    J Virol. 1988 Jun;62(6):2107-14 PMID: 2452899
  32. Complete nucleotide sequence of the AIDS virus, HTLV-III.
    Nature. 1985 Jan 24-30;313(6000):277-84 PMID: 2578615
  33. Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein.
    Proc Natl Acad Sci U S A. 1989 Sep;86(17):6768-72 PMID: 2771954
  34. Quantifying the infectivity of human immunodeficiency virus.
    Proc Natl Acad Sci U S A. 1989 Jun;86(12):4644-8 PMID: 2734313
  35. Modification of an ELISA-based procedure for affinity determination: correction necessary for use with bivalent antibody.
    Mol Immunol. 1987 Oct;24(10):1055-60 PMID: 3683403
  36. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1.
    Science. 1987 Sep 11;237(4820):1351-5 PMID: 3629244
  37. Measurements of the true affinity constant in solution of antigen-antibody complexes by enzyme-linked immunosorbent assay.
    J Immunol Methods. 1985 Mar 18;77(2):305-19 PMID: 3981007
  38. Antibody-mediated in vitro neutralization of human immunodeficiency virus type 1 abolishes infectivity for chimpanzees.
    J Virol. 1990 Aug;64(8):3674-8 PMID: 2370678
  39. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160.
    Nature. 1990 Jun 14;345(6276):622-5 PMID: 2190095
  40. Double immunocytochemical staining for in vivo detection of epitope specificity and isotype of antibody-forming cells against synthetic peptides homologous to human immunodeficiency virus-1.
    J Histochem Cytochem. 1990 Apr;38(4):457-62 PMID: 1690764
  41. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant.
    Science. 1990 Aug 24;249(4971):932-5 PMID: 2392685
  42. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells.
    J Biol Chem. 1990 Jun 25;265(18):10373-82 PMID: 2355006
  43. Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid.
    Proc Natl Acad Sci U S A. 1984 Jul;81(13):3998-4002 PMID: 6204335
  44. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS.
    Science. 1984 May 4;224(4648):497-500 PMID: 6200935
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.66.3.1823-1831.1992
Published
1992-03-00
Pages
1823-31
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC240953
Subset
IM
Grants
NIAID NIH HHS · AI-25862 · United States
NINDS NIH HHS · NS-26665 · United States
Corrections
ErratumIn
PMID: 1629971
External Links
PubMed source DOI: 10.1128/JVI.66.3.1823-1831.1992 PMC Full Text View journal details
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