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. 1987 Jun;84(11):3891–3895. doi: 10.1073/pnas.84.11.3891

Monoclonal anti-idiotypic antibody mimics the CD4 receptor and binds human immunodeficiency virus.

T C Chanh, G R Dreesman, R C Kennedy
PMCID: PMC304982  PMID: 3495801

Abstract

A monoclonal anti-idiotypic (anti-Id) antibody, HF1.7, was generated against anti-Leu-3a, a mouse monoclonal antibody (mAb) specific for the CD4 molecule on human helper/inducer T lymphocytes. The anti-Id nature of HF1.7 was demonstrated by the following properties. (i) It reacted in a solid-phase immunoassay with anti-Leu-3a and not with a panel of irrelevant mouse mAbs. (ii) It partially inhibited the binding of anti-Leu-3a to CD4+ T cells. (iii) It detected a common idiotype present on various anti-CD4 mAbs. Because the CD4 molecule represents the receptor site for human immunodeficiency virus (HIV), the etiologic viral agent of acquired immunodeficiency syndrome, we examined the ability of the anti-mAb HF1.7 to mimic CD4 and bind HIV. This anti-Id mAb reacted with HIV antigens in commercial HIV ELISAs and recognized HIV-infected human T cells but not uninfected cells when analyzed by flow cytofluorometry. Attesting further to the HIV specificity, the anti-Id mAb reacted with a recombinant gp160 peptide and a molecule of Mr 110,000-120,000 in immunoblot analysis of HIV-infected cell lysates. The anti-Id mAb also partially neutralized HIV infection of human T cells in vitro. These results strongly suggest that this anti-Id mAb mimics the CD4 antigenic determinants involved in binding to HIV.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ardman B., Khiroya R. H., Schwartz R. S. Recognition of a leukemia-related antigen by an antiidiotypic antiserum to an anti-gp70 monoclonal antibody. J Exp Med. 1985 Apr 1;161(4):669–686. doi: 10.1084/jem.161.4.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benn S., Rutledge R., Folks T., Gold J., Baker L., McCormick J., Feorino P., Piot P., Quinn T., Martin M. Genomic heterogeneity of AIDS retroviral isolates from North America and Zaire. Science. 1985 Nov 22;230(4728):949–951. doi: 10.1126/science.2997922. [DOI] [PubMed] [Google Scholar]
  3. Chanh T. C., Chen C. L., Cooper M. D. Mouse monoclonal antibodies to chicken VH idiotypic determinants reactivity with B and T cells. J Immunol. 1982 Dec;129(6):2541–2547. [PubMed] [Google Scholar]
  4. Chanh T. C., Dreesman G. R., Kanda P., Linette G. P., Sparrow J. T., Ho D. D., Kennedy R. C. Induction of anti-HIV neutralizing antibodies by synthetic peptides. EMBO J. 1986 Nov;5(11):3065–3071. doi: 10.1002/j.1460-2075.1986.tb04607.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chanh T. C., Kennedy R. C., Alderete B. E., Kanda P., Eichberg J. W., Dreesman G. R. Human immunodeficiency virus gp120 glycoprotein detected by a monoclonal antibody to a synthetic peptide. Eur J Immunol. 1986 Nov;16(11):1465–1468. doi: 10.1002/eji.1830161126. [DOI] [PubMed] [Google Scholar]
  6. Co M. S., Gaulton G. N., Fields B. N., Greene M. I. Isolation and biochemical characterization of the mammalian reovirus type 3 cell-surface receptor. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1494–1498. doi: 10.1073/pnas.82.5.1494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  8. Dichter M. A., Weiner H. L., Fields B. N., Mitchell G., Noseworthy J., Gaulton G., Greene M. Antiidiotypic antibody to reovirus binds to neurons and protects from viral infection. Ann Neurol. 1986 Jun;19(6):555–558. doi: 10.1002/ana.410190606. [DOI] [PubMed] [Google Scholar]
  9. Dreesman G. R., Kennedy R. C. Anti-idiotypic antibodies: implications of internal image-based vaccines for infectious diseases. J Infect Dis. 1985 May;151(5):761–765. doi: 10.1093/infdis/151.5.761. [DOI] [PubMed] [Google Scholar]
  10. Folks T., Benn S., Rabson A., Theodore T., Hoggan M. D., Martin M., Lightfoote M., Sell K. Characterization of a continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539–4543. doi: 10.1073/pnas.82.13.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
  13. Gaulton G. N., Greene M. I. Idiotypic mimicry of biological receptors. Annu Rev Immunol. 1986;4:253–280. doi: 10.1146/annurev.iy.04.040186.001345. [DOI] [PubMed] [Google Scholar]
  14. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  15. Kauffman R. S., Noseworthy J. H., Nepom J. T., Finberg R., Fields B. N., Greene M. I. Cell receptors for the mammalian reovirus. II. Monoclonal anti-idiotypic antibody blocks viral binding to cells. J Immunol. 1983 Nov;131(5):2539–2541. [PubMed] [Google Scholar]
  16. Kennedy R. C., Dreesman G. R., Butel J. S., Lanford R. E. Suppression of in vivo tumor formation induced by simian virus 40-transformed cells in mice receiving antiidiotypic antibodies. J Exp Med. 1985 Jun 1;161(6):1432–1449. doi: 10.1084/jem.161.6.1432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kennedy R. C., Eichberg J. W., Lanford R. E., Dreesman G. R. Anti-idiotypic antibody vaccine for type B viral hepatitis in chimpanzees. Science. 1986 Apr 11;232(4747):220–223. doi: 10.1126/science.3952505. [DOI] [PubMed] [Google Scholar]
  18. Kennedy R. C., Henkel R. D., Pauletti D., Allan J. S., Lee T. H., Essex M., Dreesman G. R. Antiserum to a synthetic peptide recognizes the HTLV-III envelope glycoprotein. Science. 1986 Mar 28;231(4745):1556–1559. doi: 10.1126/science.3006246. [DOI] [PubMed] [Google Scholar]
  19. Kennedy R. C., Melnick J. L., Dreesman G. R. Anti-idiotypes and immunity. Sci Am. 1986 Jul;255(1):48–56. doi: 10.1038/scientificamerican0786-48. [DOI] [PubMed] [Google Scholar]
  20. Klatzmann D., Barré-Sinoussi F., Nugeyre M. T., Danquet C., Vilmer E., Griscelli C., Brun-Veziret F., Rouzioux C., Gluckman J. C., Chermann J. C. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. doi: 10.1126/science.6328660. [DOI] [PubMed] [Google Scholar]
  21. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  22. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  23. McDougal J. S., Mawle A., Cort S. P., Nicholson J. K., Cross G. D., Scheppler-Campbell J. A., Hicks D., Sligh J. Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. J Immunol. 1985 Nov;135(5):3151–3162. [PubMed] [Google Scholar]
  24. McDougal J. S., Nicholson J. K., Cross G. D., Cort S. P., Kennedy M. S., Mawle A. C. Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. J Immunol. 1986 Nov 1;137(9):2937–2944. [PubMed] [Google Scholar]
  25. Nicholson J. K., Cross G. D., Callaway C. S., McDougal J. S. In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). J Immunol. 1986 Jul 1;137(1):323–329. [PubMed] [Google Scholar]
  26. Sattentau Q. J., Dalgleish A. G., Weiss R. A., Beverley P. C. Epitopes of the CD4 antigen and HIV infection. Science. 1986 Nov 28;234(4780):1120–1123. doi: 10.1126/science.2430333. [DOI] [PubMed] [Google Scholar]
  27. Wakeland E. K., Benedict A. A. Structural and genetic studies on chicken 7S immunoglobulin allotypes. I. Detection of four heavy chain specificities with a new radioimmunoassay. J Immunol. 1976 Dec;117(6):2185–2190. [PubMed] [Google Scholar]

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