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. 1987 Jul;61(3):247–254.

Cross-reactive variable-region associated epitopes of human IgG1 lambda paraprotein detected by a monoclonal antibody panel.

L C Walker, S Dhut, W M Gregory, J A Habeshaw
PMCID: PMC1453408  PMID: 2440795

Abstract

This paper describes the production and characterization of a panel of 15 mouse monoclonal antibodies selected for putative activity against V-region related or allotypic determinants of a single IgG1 lambda paraprotein obtained from a patient with malignant lymphoplasmacytoid lymphoma. The specificity of each reagent for epitopes on the heavy (H) or light (L) chain or for conformational determinants (CD) of the immunogen was determined and the ability of one reagent to compete with another for these sites investigated. The fine specificity of the antibodies was assessed by screening on a large series of normal and paraprotein-containing sera. One monoclonal showed specificity for the Glm(f) allotype. The 14 other reagents identified a minimum of nine different epitopes in the V region of the immunogen, with four antibodies detecting private conformationally determined idiotypic specificities. Eight determinants were V-region markers also expressed on other paraproteins. A total of 30 out of 159 different paraproteins cross-reacted with one or more of the antibodies. Four of the shared epitopes were lambda-chain associated, three were H-chain associated and one was a conformational determinant. Homologies of lambda chain were identified more frequently among other paraproteins than those of H chain. The relationship between epitope expression and H-chain class of paraprotein was not random. The frequency of expression of cross-reactivities in association with IgG1 proteins was always exceeded by higher frequency of epitope expression in association with other classes of H-chain isotype. The potential therapeutic value of such panels of characterized monoclonal reagents is discussed.

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Selected References

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  1. Adams J. M., Harris A. W., Pinkert C. A., Corcoran L. M., Alexander W. S., Cory S., Palmiter R. D., Brinster R. L. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985 Dec 12;318(6046):533–538. doi: 10.1038/318533a0. [DOI] [PubMed] [Google Scholar]
  2. Anderson M. L., Szajnert M. F., Kaplan J. C., McColl L., Young B. D. The isolation of a human Ig V lambda gene from a recombinant library of chromosome 22 and estimation of its copy number. Nucleic Acids Res. 1984 Sep 11;12(17):6647–6661. doi: 10.1093/nar/12.17.6647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bird P., Lowe J., Jefferis R., de Lange G., van Loghem E., Ling N. R. Monoclonal antibodies to an immunoglobulin allotype marker G1m(f). Vox Sang. 1984;47(5):366–372. doi: 10.1111/j.1423-0410.1984.tb04141.x. [DOI] [PubMed] [Google Scholar]
  4. Bluestone J. A., Sharrow S. O., Epstein S. L., Ozato K., Sachs D. H. Induction of anti-H-2 antibodies without alloantigen exposure by in vivo administration of anti-idiotype. Nature. 1981 May 21;291(5812):233–235. doi: 10.1038/291233a0. [DOI] [PubMed] [Google Scholar]
  5. Capra J. D., Kehoe J. M. Hypervariable regions, idiotypy, and the antibody-combining site. Adv Immunol. 1975;20:1–40. doi: 10.1016/s0065-2776(08)60205-9. [DOI] [PubMed] [Google Scholar]
  6. Carson D. A., Fong S. A common idiotope on human rheumatoid factors identified by a hybridoma antibody. Mol Immunol. 1983 Oct;20(10):1081–1087. doi: 10.1016/0161-5890(83)90116-5. [DOI] [PubMed] [Google Scholar]
  7. Dwyer D. S., Bradley R. J., Urquhart C. K., Kearney J. F. Naturally occurring anti-idiotypic antibodies in myasthenia gravis patients. Nature. 1983 Feb 17;301(5901):611–614. doi: 10.1038/301611a0. [DOI] [PubMed] [Google Scholar]
  8. Emmrich F., Greger B., Eichmann K. A cross-reacting human idiotype (B17) associated with antibodies to N-acetyl-D-glucosamine. Specificity, immunoglobulin class association, and distribution in the population. Eur J Immunol. 1983 Apr;13(4):273–278. doi: 10.1002/eji.1830130402. [DOI] [PubMed] [Google Scholar]
  9. Evans S. W., Feizi T., Childs R., Ling N. R. Monoclonal antibody against a cross-reactive idiotypic determinant found on human autoantibodies with anti-I and -i specificities. Mol Immunol. 1983 Oct;20(10):1127–1131. doi: 10.1016/0161-5890(83)90122-0. [DOI] [PubMed] [Google Scholar]
  10. Giardina S. L., Schroff R. W., Kipps T. J., Woodhouse C. S., Abrams P. G., Rager H. C., Morgan A. C., Jr, Foon K. A. The generation of monoclonal anti-idiotype antibodies to human B cell-derived leukemias and lymphomas. J Immunol. 1985 Jul;135(1):653–658. [PubMed] [Google Scholar]
  11. Gordon J., Abdul-Ahad A. K., Hamblin T. J., Stevenson F. K., Stevenson G. T. Mechanisms of tumour cell escape encountered in treating lymphocytic leukaemia with anti-idiotypic antibody. Br J Cancer. 1984 May;49(5):547–557. doi: 10.1038/bjc.1984.88. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hatzubai A., Maloney D. G., Levy R. The use of a monoclonal anti-idiotype antibody to study the biology of a human B cell lymphoma. J Immunol. 1981 Jun;126(6):2397–2402. [PubMed] [Google Scholar]
  13. Hawkes R., Niday E., Gordon J. A dot-immunobinding assay for monoclonal and other antibodies. Anal Biochem. 1982 Jan 1;119(1):142–147. doi: 10.1016/0003-2697(82)90677-7. [DOI] [PubMed] [Google Scholar]
  14. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  15. Kubagawa H., Vogler L. B., Capra J. D., Conrad M. E., Lawton A. R., Cooper M. D. Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation. J Exp Med. 1979 Oct 1;150(4):792–807. doi: 10.1084/jem.150.4.792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  17. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  18. Miller R. A., Maloney D. G., Warnke R., Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med. 1982 Mar 4;306(9):517–522. doi: 10.1056/NEJM198203043060906. [DOI] [PubMed] [Google Scholar]
  19. Nepom G. T., Hellström I., Hellström K. E. Suppressor mechanisms in tumor immunity. Experientia. 1983 Mar 15;39(3):235–242. doi: 10.1007/BF01955286. [DOI] [PubMed] [Google Scholar]
  20. Nepom G. T., Nelson K. A., Holbeck S. L., Hellström I., Hellström K. E. Induction of immunity to a human tumor marker by in vivo administration of anti-idiotypic antibodies in mice. Proc Natl Acad Sci U S A. 1984 May;81(9):2864–2867. doi: 10.1073/pnas.81.9.2864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Péterfy F., Kuusela P., Mäkelä O. Affinity requirements for antibody assays mapped by monoclonal antibodies. J Immunol. 1983 Apr;130(4):1809–1813. [PubMed] [Google Scholar]
  22. Raffeld M., Neckers L., Longo D. L., Cossman J. Spontaneous alteration of idiotype in a monoclonal B-cell lymphoma. Escape from detection by anti-idiotype. N Engl J Med. 1985 Jun 27;312(26):1653–1658. doi: 10.1056/NEJM198506273122601. [DOI] [PubMed] [Google Scholar]
  23. Rajewsky K., Takemori T. Genetics, expression, and function of idiotypes. Annu Rev Immunol. 1983;1:569–607. doi: 10.1146/annurev.iy.01.040183.003033. [DOI] [PubMed] [Google Scholar]
  24. Rankin E. M., Hekman A., Hardeman M. R., Hoefnagel C. A. Dynamic studies of lymphocytes labelled with indium-111 during and after treatment with monoclonal anti-idiotype antibody in advanced B cell lymphoma. Br Med J (Clin Res Ed) 1984 Oct 27;289(6452):1097–1100. doi: 10.1136/bmj.289.6452.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rivat-Peran L., Tischendorf F. W., Dumitresco S. M., Rivat C., Tischendorf M. M., Haas H., Deutsch H. F. The variable region of human immunoglobulins. I. Serologic and structural correlations of antigenic markers common to V lambda I and V lambda IV proteins (isotypic cross-reactivities). J Immunol. 1980 Jul;125(1):270–277. [PubMed] [Google Scholar]
  26. Rocca-Serra J., Tonnelle C., Fougereau M. Two monoclonal antibodies against different antigens using the same VH germ-line gene. 1983 Jul 28-Aug 3Nature. 304(5924):353–355. doi: 10.1038/304353a0. [DOI] [PubMed] [Google Scholar]
  27. Sanchez P., Juy D., Cazenave P. A. Allotypic restriction of the expression of MOPC460 idiotope after immunization with either anti-2,4-dinitrophenyl (DNP) or anti-idiotypic antibodies. Eur J Immunol. 1983 Dec;13(12):999–1003. doi: 10.1002/eji.1830131209. [DOI] [PubMed] [Google Scholar]
  28. Sklar J., Cleary M. L., Thielemans K., Gralow J., Warnke R., Levy R. Biclonal B-cell lymphoma. N Engl J Med. 1984 Jul 5;311(1):20–27. doi: 10.1056/NEJM198407053110104. [DOI] [PubMed] [Google Scholar]
  29. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Urbain J., Wikler M., Franssen J. D., Collignon C. Idiotypic regulation of the immune system by the induction of antibodies against anti-idiotypic antibodies. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5126–5130. doi: 10.1073/pnas.74.11.5126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Walsh F. S., Moore S. E., Dhut S. Monoclonal antibody to human fibronectin: production and characterization using human muscle cultures. Dev Biol. 1981 May;84(1):121–132. doi: 10.1016/0012-1606(81)90376-6. [DOI] [PubMed] [Google Scholar]
  32. Zhu D., Kim H. S., Deutsch H. F. Variable-region sequences of five human lambda-chain proteins reacting with an idiotypic antibody to the MCG Bence-Jones protein. Mol Immunol. 1983 Oct;20(10):1107–1116. doi: 10.1016/0161-5890(83)90120-7. [DOI] [PubMed] [Google Scholar]

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