Skip to main content
Immunology logoLink to Immunology
. 1988 Jun;64(2):245–251.

Human monoclonal antibodies to phenolic glycolipid-I derived from patients with leprosy, and production of specific anti-idiotypes.

M Locniskar 1, A Zumla 1, D W Mudd 1, D A Isenberg 1, W Williams 1, K P McAdam 1
PMCID: PMC1384950  PMID: 3292409

Abstract

Human monoclonal antibodies (mAb) were produced by hybridomas derived from fusion of the GM4672 lymphoblastoid cell line and peripheral blood mononuclear cells from leprosy patients. Hybridoma supernatants were screened for immunoglobulin (Ig) secretion, binding to Mycobacterium leprae, phenolic glycolipid-I (Phen GL-I), the unique M. leprae glycolipid and single-stranded(ss)DNA by ELISA. On the basis of direct-binding ELISAs, two IgMk mAb (PR4 and TH3) were selected for characterization. PR4 and TH3 bound to M. leprae, Phen GL-I and ssDNA; PR4 also bound to M. avium and M. kansasii and TH3 to M. kansasii. Inhibition assays demonstrated that these antibodies did not bind to the terminal disaccharide of Phen GL-I. In addition, both PR4 and TH3 bound to several autoantigens: ssDNA, double-stranded(ds)DNA and poly(ADP-ribose) but not RNA. PR4 and TH3 were used for preparation of rabbit anti-idiotype antisera. Inhibition studies demonstrated that the affinity purified rabbit anti-idiotype antisera were specific for their respective idiotype and that both Phen GL-I and ssDNA inhibited binding of idiotype to its anti-idiotype. PR4, but not TH3, was found to be similar but not identical to the 16/6 idiotype originally identified on a human monoclonal anti-DNA antibody derived from a patient with systemic lupus erythematosus (SLE).

Full text

PDF
251

Selected References

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

  1. André-Schwartz J., Datta S. K., Shoenfeld Y., Isenberg D. A., Stollar B. D., Schwartz R. S. Binding of cytoskeletal proteins by monoclonal anti-DNA lupus autoantibodies. Clin Immunol Immunopathol. 1984 May;31(2):261–271. doi: 10.1016/0090-1229(84)90246-0. [DOI] [PubMed] [Google Scholar]
  2. Atlaw T., Kozbor D., Roder J. C. Human monoclonal antibodies against Mycobacterium leprae. Infect Immun. 1985 Jul;49(1):104–110. doi: 10.1128/iai.49.1.104-110.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cho S. N., Hunter S. W., Gelber R. H., Rea T. H., Brennan P. J. Quantitation of the phenolic glycolipid of Mycobacterium leprae and relevance to glycolipid antigenemia in leprosy. J Infect Dis. 1986 Mar;153(3):560–569. doi: 10.1093/infdis/153.3.560. [DOI] [PubMed] [Google Scholar]
  4. Dudeney C., Shoenfeld Y., Rauch J., Jones M., Mackworth Young C., Tavassoli M., Shall S., Isenberg D. A. A study of anti-poly (ADP-ribose) antibodies and an anti-DNA antibody idiotype and other immunological abnormalities in lupus family members. Ann Rheum Dis. 1986 Jun;45(6):502–507. doi: 10.1136/ard.45.6.502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eilat D. Anti-DNA antibodies: problems in their study and interpretation. Clin Exp Immunol. 1986 Aug;65(2):215–222. [PMC free article] [PubMed] [Google Scholar]
  6. Glassy M. C., Handley H. H., Hagiwara H., Royston I. UC 729-6, a human lymphoblastoid B-cell line useful for generating antibody-secreting human-human hybridomas. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6327–6331. doi: 10.1073/pnas.80.20.6327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Harboe M., Closs O., Bjune G., Kronvall G., Axelsen N. H. Mycobacterium leprae specific antibodies detected by radioimmunoassay. Scand J Immunol. 1978;7(2):111–120. doi: 10.1111/j.1365-3083.1978.tb00433.x. [DOI] [PubMed] [Google Scholar]
  8. Mackworth-Young C., Sabbaga J., Schwartz R. S. Idiotypic markers of polyclonal B cell activation. Public idiotypes shared by monoclonal antibodies derived from patients with systemic lupus erythematosus or leprosy. J Clin Invest. 1987 Feb;79(2):572–581. doi: 10.1172/JCI112849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Rauch J., Massicotte H., Tannenbaum H. Hybridoma anti-DNA autoantibodies from patients with rheumatoid arthritis and systemic lupus erythematosus demonstrate similar nucleic acid binding characteristics. J Immunol. 1985 Jan;134(1):180–186. [PubMed] [Google Scholar]
  10. Shoenfeld Y., Hsu-Lin S. C., Gabriels J. E., Silberstein L. E., Furie B. C., Furie B., Stollar B. D., Schwartz R. S. Production of autoantibodies by human-human hybridomas. J Clin Invest. 1982 Jul;70(1):205–208. doi: 10.1172/JCI110595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Shoenfeld Y., Isenberg D. A., Rauch J., Madaio M. P., Stollar B. D., Schwartz R. S. Idiotypic cross-reactions of monoclonal human lupus autoantibodies. J Exp Med. 1983 Sep 1;158(3):718–730. doi: 10.1084/jem.158.3.718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Shoenfeld Y., Rauch J., Massicotte H., Datta S. K., André-Schwartz J., Stollar B. D., Schwartz R. S. Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med. 1983 Feb 24;308(8):414–420. doi: 10.1056/NEJM198302243080802. [DOI] [PubMed] [Google Scholar]
  13. Shoenfeld Y., Smorodinsky N. I., Lavie G., Hazaz B., Joshua H., Pinkhas J. Human lupus monoclonal autoantibodies bind to Raji cells. Immunol Lett. 1985;11(2):121–126. doi: 10.1016/0165-2478(85)90154-3. [DOI] [PubMed] [Google Scholar]
  14. Solomon G., Schiffenbauer J., Keiser H. D., Diamond B. Use of monoclonal antibodies to identify shared idiotypes on human antibodies to native DNA from patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1983 Feb;80(3):850–854. doi: 10.1073/pnas.80.3.850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Turk J. L., Bryceson A. D. Immunological phenomena in leprosy and related diseases. Adv Immunol. 1971;13:209–266. doi: 10.1016/s0065-2776(08)60185-6. [DOI] [PubMed] [Google Scholar]
  16. Young D. B., Dissanayake S., Miller R. A., Khanolkar S. R., Buchanan T. M. Humans respond predominantly with IgM immunoglobulin to the species-specific glycolipid of Mycobacterium leprae. J Infect Dis. 1984 Jun;149(6):870–873. doi: 10.1093/infdis/149.6.870. [DOI] [PubMed] [Google Scholar]
  17. Zouali M., Eyquem A. Idiotype restriction in human autoantibodies to DNA in systemic lupus erythematosus. Immunol Lett. 1984;7(4):187–190. doi: 10.1016/0165-2478(84)90041-5. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES