A VH Region Synthetic Peptide Induces Antibodies Which Bind Native Immunoglobulins and Augment an Immune Response to Antigen

  • F. A. Bonilla
  • R. S. Anderson
  • M. Z. Atassi
  • C. A. Bona

Abstract

The BALB/c myeloma protein ABPC48 (A48) binds the polysaccharide bacterial levan; its Vh is encoded by a gene derived from the VhX24 family. This antibody has been shown to crossreact idiotypically with the phosphorylcholine-binding BALB/c myeloma protein MOPC167 whose Vh shares homology with A48 from residues 32–44. We have synthesized a peptide corresponding to residues 32–44 of the Vh encoded by a germline gene of the VhX24 family. Anti-peptide antisera from rabbits were purified by affinity chromatography with peptide or intact antibody. Several myeloma proteins and monoclonal antibodies with varying degrees of homology to the peptide have been analyzed for reactivity with purified rabbit antibodies in solid-phase RIA. We observed that the specificities within rabbit antisera are heterogeneous, and that purification with antibody versus peptide yields preparations containing different specificities, albeit demonstrably peptide-related. We also show that injection of mice at birth with small amounts of purified rabbit antibodies can affect the magnitude of the response to bacterial levan and the expression of A48 idiotopes in that response.

Keywords

Rabbit Antiserum Myeloma Protein Intact Antibody Heavy Chain Variable Region Vh7183 Family 
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References

  1. Atassi, Z., Kazim, A. L. and Sakata, S. (1981) High yield coupling of peptides to protein carriers, Biochim. Biophys. Acta, 670, 300–302.PubMedCrossRefGoogle Scholar
  2. Auffray, C., Sikorav, J. L., Ollo, R. and Rougeon, F. (1981) Correlation between D region structure and antigen-binding specificity: evidences from the comparison of closely related immunoglobulin Vh sequences. Ann. Immunol. (Inst. Pasteur), 132D, 77–88.CrossRefGoogle Scholar
  3. Barak, Z. (1988) Immunochemical and molecular analysis of beta(26) fructosan binding monoclonal antibodies bearing the A48 regulatory idiotope. Doctoral dissertation, The City University of New York.Google Scholar
  4. Bona, C., Lieberman, R., Chien, C. C., Mond, J., House, S., Green, I. and Paul, W. E. (1978) Immune response to levan. I. Kinetics and ontogeny of anti-levan and anti-inulin antibody response and expression of cross-reactive idiotype. J. Immunol. 120. 1436–1442.PubMedGoogle Scholar
  5. Bona, C., Victor-Kobrin, C., Manheimer, A., Legrain, P., Buttin, G., Yancopoulos, G. and Alt, F. (1985) Genetic and molecular aspects of regulatory idiotopes. In Monoclonal Antibodies 84: Biological and Clinical Applications. Pinchera, A., Doria, G., Dammaco, F. and Bargellesi, A. eds., Editrice Kurtis s.r.l., Milan. pp. 55–75.Google Scholar
  6. Bonilla, F. A., Zaghouani, H., Rubin, M. and Bona, C. (1988) Antigen binding, idiotypy, and Vk gene usage among hybridomas selected for expression of the VhX24 gene family: immunochemical and structural analysis. (Submitted).Google Scholar
  7. Brodeur, P. M. and Riblet, R. (1984) The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes, Eur. J. Immunol., 14, 922–930.PubMedCrossRefGoogle Scholar
  8. Chen, P. P., Fong, S., Normansell, D., Houghten, R. A., Karras, J. G., Vaughan, J. H. and Carson, D. A. (1984) Delineation of a cross-reactive idiotype on human autoantibodies with antibody against a synthetic peptide, J. Exp. Med., 159, 1502–1511.PubMedCrossRefGoogle Scholar
  9. Chen, P. P., Goi, F., Fong, S., Jirik, F., Vaughan J., H., Frangione, B. and Carson, D. A. (1985) The majority of human monoclonal IgM rheumatoid factors express a “primary structure-dependent” cross-reactive idiotype. J. Immunol., 134, 3281–3285.PubMedGoogle Scholar
  10. Chen, P. P., Go i, F., Houghten, R. A., Fong, S., Goldfien, R., Vaughan, J. H., Frangione, B. and Carson, D. A. (1985) Characterization of human rheumatoid factors with seven antiidiotypes induced by synthetic hypervariable region peptides, J. Exp. Med., 162, 487–500.PubMedCrossRefGoogle Scholar
  11. Chen, P. P., Houghten, R. A., Fong, S., Rhodes, G. H., Gilbertson, T. A., Vaughan, J. H., Lerner, R. A. and Carson D. A. (1984) Anti-hypervariable region antibody induced by a defined peptide: an approach for studying the structural correlates of idiotypes, Proc. Natl. Acad. Sci. USA, 81, 1784–1788.PubMedCrossRefGoogle Scholar
  12. Goldberg, B., Paul, W. E. and Bona, C. (1983) Idiotype-antiidiotype regulation. IV. Expression of common regulatory idiotopes on fructosan-binding and non-fructosan-binding monoclonal immunoglobulin, J. Exp. Med., 158, 515–528.PubMedCrossRefGoogle Scholar
  13. Goldfien, R. D., Chen, P. P., Fong, S. and Carson, D. A. (1985) Synthetic peptides corresponding to third hypervariable region of human monoclonal IgM rheumatoid factor heavy chains define an immunodominant idiotype, J. Exp. Med., 162, 756–761.PubMedCrossRefGoogle Scholar
  14. Go i, F., Chen, P. P., Pons-Estel, B., Carson, D. A. and Frangione, B. (1985) Sequence similarities and cross-idiotypic specificity of L chains among human monoclonal IgM-kappa with anti-gamma-globulin activity, J. Immunol., 135, 4073–4078.Google Scholar
  15. Hammerling, U. and Westphal, O. (1967) Synthesis and use of 0stearoyl polysaccharides in passive hemagglutination and hemolysis, Eur. J. Biochem., 1, 46–52.PubMedCrossRefGoogle Scholar
  16. Hartman, A. B. and Rudikoff, S. (1984) Vh genes encoding the immune response to beta (1, 6) -galactan : somatic mutation in IgM molecules. EMBO J. 3, 3023–3030.PubMedGoogle Scholar
  17. Hiernaux, J., Bona, C. and Baker, P. J. (1981) Neonatal treatment with low doses of anti-idiotypic antibody leads to the expression of a silent clone. J. Exp. Med., 153, 1004–1008.PubMedCrossRefGoogle Scholar
  18. Jerne, N. K. (1974) Towards a network theory of the immune system. Ann. Immunol. (Inst. Pasteur) , 125C, 373–389.Google Scholar
  19. Kabat, E. A., Wu, T. T., Reid-Miller, M., Perry, H. M. and Got-tesman, K. S. (1987) Sequences of Proteins of Immunological Interest. Fourth edition. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health.Google Scholar
  20. Kennedy, R. C., Henkel, R. D., Pauletti, D., Allan, J. S., Lee, T. H., Essex, M., and Dreesman, G. R. (1986) Antiserum to a synthetic peptide recognizes the HTLV III envelope glycopro-tein. Science, 231:1556–1559.PubMedCrossRefGoogle Scholar
  21. Koketsu, J. and Atassi, M. Z. (1974) Immunochemistry of sperm-whale myoglobin-XVI: accurate delineation of the single region in sequence 1–55 by immunochemical studies of syn-thetic peptides. Some conclusions concerning antigenic structures of proteins. Immunochemistry, 11, 1–8.PubMedCrossRefGoogle Scholar
  22. Legrain, P. and Buttin, G. (1983) ABPC 48 cross-reactive idio-topes in BALB/c mice. Natural and levan-induced expres-sion. J. Exp. Med., 158:872–884.PubMedCrossRefGoogle Scholar
  23. Legrain, P. and Buttin, G. (1985) The Vk gene expressed by BALB/c ABPC48 cross-reactive idiotypes induced by antiidio-typic immunization is identical to that of BALB/c anti-ox-azolone and A/J anti-arsonate antibodies. J. Immunol., 134, 3468–3473.PubMedGoogle Scholar
  24. Legrain, P., Voegle, D., Buttin, G. and Cazenave, P. A. (1981) Idiotype-anti-idiotype interactions and the control of the anti-beta (2–6) polyfructosan response in the mouse: speci-ficity and idiotypy of anti-ABPC48 anti-idiotypic monoclon-al antibodies. Eur. J. Immunol., 11, 678–685.PubMedCrossRefGoogle Scholar
  25. Lieberman, R., Potter, M., Humphrey, W., Jr. and Chien, C. C. (1976) Idiotypes of inulin-binding antibodies and myeloma proteins controlled by genes linked to the allotype locus of the mouse. J. Immunol., 117, 2105–2111.PubMedGoogle Scholar
  26. Lieberman, R., Potter, M., Humphrey, W., Jr., Mushinski, E. B. and Vrana, M. (1975) Multiple individual and cross-reactive idiotypes on 13 levan-binding myeloma proteins of BALB/c mice. J. Exp. Med., 142, 106–118.PubMedCrossRefGoogle Scholar
  27. McMillan, S., Seiden, M. V., Houghten, R. A., Clevinger, B., Davie, J. M. and Lerner, R. A. (1983) Synthetic idiotypes: the third hypervariable region of murine anti-dextran anti-bodies. Cell, 35, 859–863.PubMedCrossRefGoogle Scholar
  28. Moran, T., Liu, Y. C., Schulman, J. L. and Bona, C. A. (1984) Shared idiotopes among monoclonal antibodies specific for A/PR/8/34 (H1N1) and X-31 (H3N2) influenza viruses. Proc. Natl. Acad. Sci. USA, 81, 1809–1812.PubMedCrossRefGoogle Scholar
  29. Ollo, R., Auffray, C., Sikorav, J. L. and Rougeon, F. (1981) Mouse heavy chain variable regions: nucleotide sequence of a germline Vh gene segment. Nucl. Acids Res., 9, 4099–4109.PubMedCrossRefGoogle Scholar
  30. Potter, M., Newell, J. B., Rudikoff, S. and Haber, E. (1982) Classification of mouse Vk groups based on the partial amino acid sequence to the first invariant tryptophan: impact of 14 new sequences from IgG myeloma proteins. Mol. Immunol., 19, 1619–1630.PubMedCrossRefGoogle Scholar
  31. Reale, M. A., Manheimer, A. J., Moran, T. M., Norton, G., Bona, C. A. and Schulman, J. L. (1986) Characterization of monoclonal antibodies specific for sequential influenza A/PR/8/34 virus variants. J. Immunol., 137, 1352–1358.PubMedGoogle Scholar
  32. Rubinstein, L. J., Goldberg, B., Hiernaux, J., Stein, K. E. and Bona, C. (1983) Idiotype antiidiotype regulation. V. The requirement for immunization with antigen or monoclonal antiidiotypic antibodies for the activation of beta2–6 and beta2–1 polyfructosan-reactive clones in BALB/c mice treated at birth with minute amounts of anti-A48 idiotype antibodies. J. Exp. Med., 158 1129–1144PubMedCrossRefGoogle Scholar
  33. Rubinstein, L. J., Yeh, M. and Bona, C. (1982) Idiotype-antiidiotype network. II. Activation of silent clones by treatment at birth with idiotypes is associated with the expansion of idiotype-specific helper T cells. J. Exp. Med., 156, 506–521.PubMedCrossRefGoogle Scholar
  34. Rudikoff, S. and Potter, M. (1976) Size differences among immunoglobulin heavy chains from phosphorylcholine-binding proteins. Proc. Natl. Acad. Sci. USA. 73. 2109–2112PubMedCrossRefGoogle Scholar
  35. Seiden, M. V., Heuckeroth, R., Clevinger, B. , McMillan, S., Lerner, R. and Davie, J. M. (1986) Hypervariable region peptides variably induce specific anti-idiotypic antibodies: an approach to determining antigenic dominance. J. Immunol., 136. 582–587.PubMedGoogle Scholar
  36. Victor-Kobrin, C., Bonilla, F. A., Bellon, B. and Bona, C. A. (1985) Immunochemical and molecular characterization of regulatory idiotopes expressed by monoclonal antibodies exhibiting or lacking beta2–6 fructosan binding activity. J. Exp. Med., 162, 647–662.PubMedCrossRefGoogle Scholar
  37. Zaghouani, H., Bonilla, F. A., Meek, K. and Bona, C. (1988) Molecular basis for expression of the A48 regulatory idiotope on antibodies encoded by V genes from various families. (Submitted).Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • F. A. Bonilla
    • 1
  • R. S. Anderson
    • 2
  • M. Z. Atassi
    • 2
  • C. A. Bona
    • 1
  1. 1.Department of MicrobiologyThe Mount Sinai School of Medicine of The City University of New YorkNew YorkUSA
  2. 2.Department of BiochemistryBaylor College of MedicineHoustonUSA

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