Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Jul;84(14):4994–4998. doi: 10.1073/pnas.84.14.4994

Specific cellular immune response and neutralizing antibodies in goats immunized with native or recombinant envelope proteins derived from human T-lymphotropic virus type IIIB and in human immunodeficiency virus-infected men.

K Krohn, W G Robey, S Putney, L Arthur, P Nara, P Fischinger, R C Gallo, F Wong-Staal, A Ranki
PMCID: PMC305233  PMID: 2440037

Abstract

Animals immunized with native or recombinant envelope proteins from the human immunodeficiency virus (HIV, formerly referred to as human T-lymphotropic virus type III) human T-lymphotropic virus type IIIB and naturally HIV-infected men were assessed for neutralizing antibodies and cell-mediated immunity toward the virus. Immunization of rabbits or goats with the native external envelope glycoprotein gp120 or with corresponding recombinant proteins elicited strictly type-specific neutralizing antibodies. A broad, group-specific cellular immune response to gp120 and to three different HIV isolates was seen in goats immunized with the native gp120 but not in animals immunized with the nonglycosylated recombinant envelope proteins. In HIV-infected people, no T-cell response was seen, even though their T-cell response toward other foreign antigens was intact. The results show type- and group-specific epitopes on gp120, some of which may be of importance for the development of a vaccine against HIV infection.

Full text

PDF
4995

Images in this article

Selected References

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

  1. Ashorn R. G., Räsänen L., Marnela K. M., Krohn K. J. Human transfer factor in vitro. II. Augmentation of the secretion of leucocyte migration inhibitory factor (LIF) by leucocyte dialysate and by its components L-serine and glycine. Clin Exp Immunol. 1979 Jul;37(1):50–57. [PMC free article] [PubMed] [Google Scholar]
  2. Bach M. A., Phan-Dinh-Tuy F., Bach J. F., Wallach D., Biddison W. E., Sharrow S. O., Goldstein G., Kung P. C. Unusual phenotypes of human inducer T cells as measured by OKT4 and related monoclonal antibodies. J Immunol. 1981 Sep;127(3):980–982. [PubMed] [Google Scholar]
  3. Cease K. B., Margalit H., Cornette J. L., Putney S. D., Robey W. G., Ouyang C., Streicher H. Z., Fischinger P. J., Gallo R. C., DeLisi C. Helper T-cell antigenic site identification in the acquired immunodeficiency syndrome virus gp120 envelope protein and induction of immunity in mice to the native protein using a 16-residue synthetic peptide. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4249–4253. doi: 10.1073/pnas.84.12.4249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cianciolo G. J., Copeland T. D., Oroszlan S., Snyderman R. Inhibition of lymphocyte proliferation by a synthetic peptide homologous to retroviral envelope proteins. Science. 1985 Oct 25;230(4724):453–455. doi: 10.1126/science.2996136. [DOI] [PubMed] [Google Scholar]
  5. DeLisi C., Berzofsky J. A. T-cell antigenic sites tend to be amphipathic structures. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7048–7052. doi: 10.1073/pnas.82.20.7048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Doherty P. C., Zinkernagel R. M. H-2 compatibility is required for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. J Exp Med. 1975 Feb 1;141(2):502–507. doi: 10.1084/jem.141.2.502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hahn B. H., Gonda M. A., Shaw G. M., Popovic M., Hoxie J. A., Gallo R. C., Wong-Staal F. Genomic diversity of the acquired immune deficiency syndrome virus HTLV-III: different viruses exhibit greatest divergence in their envelope genes. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4813–4817. doi: 10.1073/pnas.82.14.4813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Krohn K., Ranki A., Antonen J., Valle S. L., Suni J., Vaheri A., Saxinger C., Gallo R. C. Immune functions in homosexual men with antibodies to HTLV-III in Finland. Clin Exp Immunol. 1985 Apr;60(1):17–24. [PMC free article] [PubMed] [Google Scholar]
  9. Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell. 1986 Nov 7;47(3):333–348. doi: 10.1016/0092-8674(86)90590-8. [DOI] [PubMed] [Google Scholar]
  10. Matthews T. J., Langlois A. J., Robey W. G., Chang N. T., Gallo R. C., Fischinger P. J., Bolognesi D. P. Restricted neutralization of divergent human T-lymphotropic virus type III isolates by antibodies to the major envelope glycoprotein. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9709–9713. doi: 10.1073/pnas.83.24.9709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Miller L. H., Howard R. J., Carter R., Good M. F., Nussenzweig V., Nussenzweig R. S. Research toward malaria vaccines. Science. 1986 Dec 12;234(4782):1349–1356. doi: 10.1126/science.2431481. [DOI] [PubMed] [Google Scholar]
  13. Mitsuya H., Broder S. Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1911–1915. doi: 10.1073/pnas.83.6.1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mitsuya H., Guo H. G., Cossman J., Megson M., Reitz M. S., Jr, Broder S. Functional properties of antigen-specific T cells infected by human T-cell leukemia-lymphoma virus (HTLV-I). Science. 1984 Sep 28;225(4669):1484–1486. doi: 10.1126/science.6206569. [DOI] [PubMed] [Google Scholar]
  15. Orosz C. G., Zinn N. E., Olsen R. G., Mathes L. E. Retrovirus-mediated immunosuppression. I. FeLV-UV and specific FeLV proteins alter T lymphocyte behavior by inducing hyporesponsiveness to lymphokines. J Immunol. 1985 May;134(5):3396–3403. [PubMed] [Google Scholar]
  16. Pahwa S., Pahwa R., Saxinger C., Gallo R. C., Good R. A. Influence of the human T-lymphotropic virus/lymphadenopathy-associated virus on functions of human lymphocytes: evidence for immunosuppressive effects and polyclonal B-cell activation by banded viral preparations. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8198–8202. doi: 10.1073/pnas.82.23.8198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. 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. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  18. Putney S. D., Matthews T. J., Robey W. G., Lynn D. L., Robert-Guroff M., Mueller W. T., Langlois A. J., Ghrayeb J., Petteway S. R., Jr, Weinhold K. J. HTLV-III/LAV-neutralizing antibodies to an E. coli-produced fragment of the virus envelope. Science. 1986 Dec 12;234(4782):1392–1395. doi: 10.1126/science.2431482. [DOI] [PubMed] [Google Scholar]
  19. Quinn T. C., Mann J. M., Curran J. W., Piot P. AIDS in Africa: an epidemiologic paradigm. Science. 1986 Nov 21;234(4779):955–963. doi: 10.1126/science.3022379. [DOI] [PubMed] [Google Scholar]
  20. Rasheed S., Norman G. L., Gill P. S., Meyer P. R., Cheng L., Levine A. M. Virus-neutralizing activity, serologic heterogeneity, and retrovirus isolation from homosexual men in the Los Angeles area. Virology. 1986 Apr 15;150(1):1–9. doi: 10.1016/0042-6822(86)90260-6. [DOI] [PubMed] [Google Scholar]
  21. Robert-Guroff M., Brown M., Gallo R. C. HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex. Nature. 1985 Jul 4;316(6023):72–74. doi: 10.1038/316072a0. [DOI] [PubMed] [Google Scholar]
  22. Robey W. G., Arthur L. O., Matthews T. J., Langlois A., Copeland T. D., Lerche N. W., Oroszlan S., Bolognesi D. P., Gilden R. V., Fischinger P. J. Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7023–7027. doi: 10.1073/pnas.83.18.7023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sarngadharan M. G., Popovic M., Bruch L., Schüpbach J., Gallo R. C. Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science. 1984 May 4;224(4648):506–508. doi: 10.1126/science.6324345. [DOI] [PubMed] [Google Scholar]
  24. Starcich B. R., Hahn B. H., Shaw G. M., McNeely P. D., Modrow S., Wolf H., Parks E. S., Parks W. P., Josephs S. F., Gallo R. C. Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell. 1986 Jun 6;45(5):637–648. doi: 10.1016/0092-8674(86)90778-6. [DOI] [PubMed] [Google Scholar]
  25. Wahren B., Morfeldt-Månsson L., Biberfeld G., Moberg L., Ljungman P., Nordlund S., Bredberg-Rådén U., Werner A., Löwer J., Kurth R. Impaired specific cellular response to HTLV-III before other immune defects in patients with HTLV-III infection. N Engl J Med. 1986 Aug 7;315(6):393–394. [PubMed] [Google Scholar]
  26. Weiss R. A., Clapham P. R., Weber J. N., Dalgleish A. G., Lasky L. A., Berman P. W. Variable and conserved neutralization antigens of human immunodeficiency virus. Nature. 1986 Dec 11;324(6097):572–575. doi: 10.1038/324572a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES