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. 1992 Aug;89(2):290–295. doi: 10.1111/j.1365-2249.1992.tb06947.x

Human MoAbs produced from normal, HIV-1-negative donors and specific for glycoprotein gp120 of the HIV-1 envelope.

M Ohlin 1, J Hinkula 1, P A Broliden 1, R Grunow 1, C A Borrebaeck 1, B Wahren 1
PMCID: PMC1554443  PMID: 1379134

Abstract

Human MoAbs of IgM class were developed against three regions of the HIV-1 envelope. Uninfected donor lymphocytes were immunized in vitro with recombinant protein pB1. Four out of five antibodies were directed to different parts of the V3 region, which contains a major neutralizing site. Two out of these antibodies were directed to more than one amino acid sequence, indicating reactivity to discontinuous sites. Two of the human MoAbs inhibited viral spread between cells in tissue culture, interpreted as reactivities to conserved amino acid sequences exposed during viral maturation. No MoAb neutralized virus, which may be explained by the relatively low avidity of the antibodies. One MoAb was directed to a region containing amino acids participating in CD4 binding. This technique appears to allow formation of antibodies with fine specificities other than those obtained in infected hosts.

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Selected References

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  1. Akerblom L., Hinkula J., Broliden P. A., Mäkitalo B., Fridberger T., Rosen J., Villacres-Eriksson M., Morein B., Wahren B. Neutralizing cross-reactive and non-neutralizing monoclonal antibodies to HIV-1 gp120. AIDS. 1990 Oct;4(10):953–960. doi: 10.1097/00002030-199010000-00002. [DOI] [PubMed] [Google Scholar]
  2. Amadori A., Ciminale V., Calabro M. L., Tessarollo L., Francavilla E., Chieco-Bianchi L. Human monoclonal antibody against a gag-coded protein of human immunodeficiency virus produced by a stable EBV-transformed cell clone. AIDS Res Hum Retroviruses. 1989 Feb;5(1):73–78. doi: 10.1089/aid.1989.5.73. [DOI] [PubMed] [Google Scholar]
  3. Banapour B., Rosenthal K., Rabin L., Sharma V., Young L., Fernandez J., Engleman E., McGrath M., Reyes G., Lifson J. Characterization and epitope mapping of a human monoclonal antibody reactive with the envelope glycoprotein of human immunodeficiency virus. J Immunol. 1987 Dec 15;139(12):4027–4033. [PubMed] [Google Scholar]
  4. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  5. Borrebaeck C. A., Danielsson L., Möller S. A. Human monoclonal antibodies produced by primary in vitro immunization of peripheral blood lymphocytes. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3995–3999. doi: 10.1073/pnas.85.11.3995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Borrebaeck C. A. Strategy for the production of human monoclonal antibodies using in vitro activated B cells. J Immunol Methods. 1989 Oct 24;123(2):157–165. doi: 10.1016/0022-1759(89)90219-6. [DOI] [PubMed] [Google Scholar]
  7. Broliden P. A., Ljunggren K., Hinkula J., Norrby E., Akerblom L., Wahren B. A monoclonal antibody to human immunodeficiency virus type 1 which mediates cellular cytotoxicity and neutralization. J Virol. 1990 Feb;64(2):936–940. doi: 10.1128/jvi.64.2.936-940.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Broliden P. A., Moschese V., Ljunggren K., Rosen J., Fundaro C., Plebani A., Jondal M., Rossi P., Wahren B. Diagnostic implication of specific immunoglobulin G patterns of children born to HIV-infected mothers. AIDS. 1989 Sep;3(9):577–582. doi: 10.1097/00002030-198909000-00004. [DOI] [PubMed] [Google Scholar]
  9. Broliden P. A., Mäkitalo B., Akerblom L., Rosen J., Broliden K., Utter G., Jondal M., Norrby E., Wahren B. Identification of amino acids in the V3 region of gp120 critical for virus neutralization by human HIV-1-specific antibodies. Immunology. 1991 Aug;73(4):371–376. [PMC free article] [PubMed] [Google Scholar]
  10. Carroll W. L., Thielemans K., Dilley J., Levy R. Mouse x human heterohybridomas as fusion partners with human B cell tumors. J Immunol Methods. 1986 May 1;89(1):61–72. doi: 10.1016/0022-1759(86)90032-3. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Danielsson L., Furebring C., Ohlin M., Hultman L., Abrahamson M., Carlsson R., Borrebaeck C. A. Human monoclonal antibodies with different fine specificity for digoxin derivatives: cloning of heavy and light chain variable region sequences. Immunology. 1991 Sep;74(1):50–54. [PMC free article] [PubMed] [Google Scholar]
  13. Desgranges C., Boyer V., Souche S., Sprecher S., Burney A., Gallo R. C., Bernard J., Reveil B., Zagury D. Monoclonal antibodies to HIV in a non-infected, immunised volunteer. Lancet. 1988 Apr 23;1(8591):935–936. doi: 10.1016/s0140-6736(88)91737-0. [DOI] [PubMed] [Google Scholar]
  14. Evans L. A., Homsy J. M., Morrow W. J., Gaston I., Sooy C. D., Levy J. A. Human monoclonal antibody directed against gag gene products of the human immunodeficiency virus. J Immunol. 1988 Feb 1;140(3):941–943. [PubMed] [Google Scholar]
  15. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  16. Gorny M. K., Gianakakos V., Sharpe S., Zolla-Pazner S. Generation of human monoclonal antibodies to human immunodeficiency virus. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1624–1628. doi: 10.1073/pnas.86.5.1624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Goudsmit J., Debouck C., Meloen R. H., Smit L., Bakker M., Asher D. M., Wolff A. V., Gibbs C. J., Jr, Gajdusek D. C. 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):4478–4482. doi: 10.1073/pnas.85.12.4478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Grunow R., Jahn S., Porstmann T., Kiessig S. S., Steinkellner H., Steindl F., Mattanovich D., Gürtler L., Deinhardt F., Katinger H. The high efficiency, human B cell immortalizing heteromyeloma CB-F7. Production of human monoclonal antibodies to human immunodeficiency virus. J Immunol Methods. 1988 Feb 10;106(2):257–265. doi: 10.1016/0022-1759(88)90206-2. [DOI] [PubMed] [Google Scholar]
  19. Hammar L., Gilljam G. Extraction of HIV-1 in aqueous two-phase systems to obtain a high yield of gp120. AIDS Res Hum Retroviruses. 1990 Dec;6(12):1379–1388. doi: 10.1089/aid.1990.6.1379. [DOI] [PubMed] [Google Scholar]
  20. Hedman K., Seppälä I. Recent rubella virus infection indicated by a low avidity of specific IgG. J Clin Immunol. 1988 May;8(3):214–221. doi: 10.1007/BF00917569. [DOI] [PubMed] [Google Scholar]
  21. Hinkula J., Rosen J., Sundqvist V. A., Stigbrand T., Wahren B. Epitope mapping of the HIV-1 gag region with monoclonal antibodies. Mol Immunol. 1990 May;27(5):395–403. doi: 10.1016/0161-5890(90)90163-t. [DOI] [PubMed] [Google Scholar]
  22. Ho D. D., Kaplan J. C., Rackauskas I. E., Gurney M. E. Second conserved domain of gp120 is important for HIV infectivity and antibody neutralization. Science. 1988 Feb 26;239(4843):1021–1023. doi: 10.1126/science.2830667. [DOI] [PubMed] [Google Scholar]
  23. Ho D. D., McKeating J. A., Li X. L., Moudgil T., Daar E. S., Sun N. C., Robinson J. E. Conformational epitope on gp120 important in CD4 binding and human immunodeficiency virus type 1 neutralization identified by a human monoclonal antibody. J Virol. 1991 Jan;65(1):489–493. doi: 10.1128/jvi.65.1.489-493.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hunter M. M., Margolies M. N., Ju A., Haber E. High-affinity monoclonal antibodies to the cardiac glycoside, digoxin. J Immunol. 1982 Sep;129(3):1165–1172. [PubMed] [Google Scholar]
  25. Javaherian K., Langlois A. J., McDanal C., Ross K. L., Eckler L. I., Jellis C. L., Profy A. T., Rusche J. R., Bolognesi D. P., Putney S. D. Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6768–6772. doi: 10.1073/pnas.86.17.6768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kenealy W. R., Matthews T. J., Ganfield M. C., Langlois A. J., Waselefsky D. M., Petteway S. R., Jr Antibodies from human immunodeficiency virus-infected individuals bind to a short amino acid sequence that elicits neutralizing antibodies in animals. AIDS Res Hum Retroviruses. 1989 Apr;5(2):173–182. doi: 10.1089/aid.1989.5.173. [DOI] [PubMed] [Google Scholar]
  27. Kennedy R. C., Dreesman G. R., Chanh T. C., Boswell R. N., Allan J. S., Lee T. H., Essex M., Sparrow J. T., Ho D. D., Kanda P. Use of a resin-bound synthetic peptide for identifying a neutralizing antigenic determinant associated with the human immunodeficiency virus envelope. J Biol Chem. 1987 Apr 25;262(12):5769–5774. [PubMed] [Google Scholar]
  28. Koshida R., Cox S., Harmenberg J., Gilljam G., Wahren B. Structure-activity relationships of fluorinated nucleoside analogs and their synergistic effect in combination with phosphonoformate against human immunodeficiency virus type 1. Antimicrob Agents Chemother. 1989 Dec;33(12):2083–2088. doi: 10.1128/aac.33.12.2083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. LaRosa G. J., Davide J. P., Weinhold K., Waterbury J. A., Profy A. T., Lewis J. A., Langlois A. J., Dreesman G. R., Boswell R. N., Shadduck P. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science. 1990 Aug 24;249(4971):932–935. doi: 10.1126/science.2392685. [DOI] [PubMed] [Google Scholar]
  30. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987 Sep 11;50(6):975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [PubMed] [Google Scholar]
  31. Leonard C. K., Spellman M. W., Riddle L., Harris R. J., Thomas J. N., Gregory T. J. 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):10373–10382. [PubMed] [Google Scholar]
  32. Liou R. S., Rosen E. M., Fung M. S., Sun W. N., Sun C., Gordon W., Chang N. T., Chang T. W. A chimeric mouse-human antibody that retains specificity for HIV gp120 and mediates the lysis of HIV-infected cells. J Immunol. 1989 Dec 15;143(12):3967–3975. [PubMed] [Google Scholar]
  33. Ljunggren K., Fenyö E. M., Biberfeld G., Jondal M. Detection of antibodies which mediate human immunodeficiency virus-specific cellular cytotoxicity (ADCC) in vitro. J Immunol Methods. 1987 Nov 23;104(1-2):7–14. doi: 10.1016/0022-1759(87)90481-9. [DOI] [PubMed] [Google Scholar]
  34. Mathiesen T., Broliden P. A., Rosen J., Wahren B. Mapping of IgG subclass and T-cell epitopes on HIV proteins by synthetic peptides. Immunology. 1989 Aug;67(4):453–459. [PMC free article] [PubMed] [Google Scholar]
  35. Matsushita S., Robert-Guroff M., Rusche J., Koito A., Hattori T., Hoshino H., Javaherian K., Takatsuki K., Putney S. Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope. J Virol. 1988 Jun;62(6):2107–2114. doi: 10.1128/jvi.62.6.2107-2114.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ohlin M., Broliden P. A., Danielsson L., Wahren B., Rosen J., Jondal M., Borrebaeck C. A. Human monoclonal antibodies against a recombinant HIV envelope antigen produced by primary in vitro immunization. Characterization and epitope mapping. Immunology. 1989 Nov;68(3):325–331. [PMC free article] [PubMed] [Google Scholar]
  37. Palker T. J., Clark M. E., Langlois A. J., Matthews T. J., Weinhold K. J., Randall R. R., Bolognesi D. P., Haynes B. F. Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1932–1936. doi: 10.1073/pnas.85.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Pollock B. J., McKenzie A. S., Kemp B. E., McPhee D. A., D'Apice A. J. Human monoclonal antibodies to HIV-1: cross-reactions with gag and env products. Clin Exp Immunol. 1989 Dec;78(3):323–328. [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. 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]
  41. Robinson W. E., Jr, Kawamura T., Gorny M. K., Lake D., Xu J. Y., Matsumoto Y., Sugano T., Masuho Y., Mitchell W. M., Hersh E. Human monoclonal antibodies to the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 enhance HIV-1 infection in vitro. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3185–3189. doi: 10.1073/pnas.87.8.3185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rossi P., Moschese V., Broliden P. A., Fundaró C., Quinti I., Plebani A., Giaquinto C., Tovo P. A., Ljunggren K., Rosen J. Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein gp120 epitopes correlates with the uninfected status of children born to seropositive mothers. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8055–8058. doi: 10.1073/pnas.86.20.8055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Rusche J. R., Javaherian K., McDanal C., Petro J., Lynn D. L., Grimaila R., Langlois A., Gallo R. C., Arthur L. O., Fischinger P. J. 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):3198–3202. doi: 10.1073/pnas.85.9.3198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schwartz O., Henin Y., Marechal V., Montagnier L. A rapid and simple colorimetric test for the study of anti-HIV agents. AIDS Res Hum Retroviruses. 1988 Dec;4(6):441–448. doi: 10.1089/aid.1988.4.441. [DOI] [PubMed] [Google Scholar]
  45. Scott C. F., Jr, Silver S., Profy A. T., Putney S. D., Langlois A., Weinhold K., Robinson J. E. 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):8597–8601. doi: 10.1073/pnas.87.21.8597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Skinner M. A., Ting R., Langlois A. J., Weinhold K. J., Lyerly H. K., Javaherian K., Matthews T. J. Characteristics of a neutralizing monoclonal antibody to the HIV envelope glycoprotein. AIDS Res Hum Retroviruses. 1988 Jun;4(3):187–197. doi: 10.1089/aid.1988.4.187. [DOI] [PubMed] [Google Scholar]
  47. Smith D. H., Byrn R. A., Marsters S. A., Gregory T., Groopman J. E., Capon D. J. Blocking of HIV-1 infectivity by a soluble, secreted form of the CD4 antigen. Science. 1987 Dec 18;238(4834):1704–1707. doi: 10.1126/science.3500514. [DOI] [PubMed] [Google Scholar]
  48. Sugano T., Masuho Y., Matsumoto Y., Lake D., Gschwind C., Petersen E. A., Hersh E. M. Human monoclonal antibody against glycoproteins of human immunodeficiency virus. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1105–1112. doi: 10.1016/s0006-291x(88)81254-3. [DOI] [PubMed] [Google Scholar]
  49. Sun N. C., Ho D. D., Sun C. R., Liou R. S., Gordon W., Fung M. S., Li X. L., Ting R. C., Lee T. H., Chang N. T. Generation and characterization of monoclonal antibodies to the putative CD4-binding domain of human immunodeficiency virus type 1 gp120. J Virol. 1989 Sep;63(9):3579–3585. doi: 10.1128/jvi.63.9.3579-3585.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Sundqvist V. A., Albert J., Ohlsson E., Hinkula J., Fenyö E. M., Wahren B. Human immunodeficiency virus type 1 p24 production and antigenic variation in tissue culture of isolates with various growth characteristics. J Med Virol. 1989 Nov;29(3):170–175. doi: 10.1002/jmv.1890290305. [DOI] [PubMed] [Google Scholar]
  51. Wahren B., Rosen J., Sandström E., Mathiesen T., Modrow S., Wigzell H. HIV-1 peptides induce a proliferative response in lymphocytes from infected persons. J Acquir Immune Defic Syndr. 1989;2(5):448–456. [PubMed] [Google Scholar]
  52. Weiss R. A., Clapham P. R., Cheingsong-Popov R., Dalgleish A. G., Carne C. A., Weller I. V., Tedder R. S. Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients. Nature. 1985 Jul 4;316(6023):69–72. doi: 10.1038/316069a0. [DOI] [PubMed] [Google Scholar]

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