Development of Vaccines by Grafting Microbial Epitopes in Immunoglobulins

  • Constantin A. Bona


The variable regions (V) of immunoglobulin (Ig) bear antigenic determinants that can stimulate both B and T lymphocytes. There is solid evidence that such antigenic determinants and particularly the idiotypes, which are phenotypic marker of V genes stimulate the expansion of B cells producing anti-Id antibodies in xenogeneic (Kunkel et al., 1963), allogenic (Oudin and Michel, 1963) and autologous (Rodkey, 1974) systems as well as idiotype specific T cells (Eichman and Rajewsky, 1975; Bona et al., 1979). The expression of idiotypes usually correlates with aminoacid sequences within CDR loops of V regions of Ig molecules (Capra et al., 1977; Rudikoff et al., 1983).


Influenza Virus Cell Epitope 2PK3 Cell Internal Image Foreign Epitope 
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  1. Bastin, J., Rothbard, J., Davey, J., Jones, I., and Townsend, A. (1987). Use of synthetic peptides of influenza nucleoprotein to define epitpoes recognized by class I-restricted cytotoxic T lymphocytes. J. Exp. Med. 165: 1508.PubMedCrossRefGoogle Scholar
  2. Battegay, M., Dehen, S., Schultz, M., Hengartener, H., Zinkernagel, R.M. (1992). Vaccination with a synthetic peptide modulates lymphocytic choriomeningities virus-mediated immunopathology. J. Virol. 66: 1119–1201.Google Scholar
  3. Biletta, R., Hollingdale, M.R., and Zanetti, M. (1991). Immunogenicity of an engineered internal image antibody. Proc. Natl. Acad Sci. 88: 4713–4717.CrossRefGoogle Scholar
  4. Bogen, B., Jorgensen, T., and Hannested, K. (1985). T helper cell recognition of idiotopes on λ2 light chains of M315 and%952: evidence for dependence on somatic mutation in the third hypervariable region. Eur. J. Immunol. 15: 278–281.PubMedCrossRefGoogle Scholar
  5. Bona, C., Hooghe, R., Cazenave, P-A., LeGuern, C., and Paul, W.E. (1979). Cellular basis of regulation of expression of idiotypes II. Immunity to anti-MOPC460 idiotype antibodies increases the level of anti-trinitrophenyl antibodies bearing 460 idiotypes. J. Exp. Med. 149: 815–823.PubMedCrossRefGoogle Scholar
  6. Bona, C. (1988). Anti-idiotypes in biological applications of anti-idiotypes (ed. C. Bona). Vol. 1, pp 1–13 CRC Press, Boca Raton, Florida.Google Scholar
  7. Braciale, T.L., Braciale, V.L. (1992). Antigen presentation structural themes and functional variations. Immunol. Today 12: 124–129.CrossRefGoogle Scholar
  8. Bruck, C., Co, S.M, Slaoui, M., Gaulton, G.N., Smith, T., Fields, B.M., Mullins, J.I. and M.I., Green (1986). Nucleic acid sequence of an internal image-bearing monoclonal anti-idiotype and its comparison to the sequence of the external antigen. Proc. Natl. Acad. Sci., 6578-6582.Google Scholar
  9. Brumeanu, T.D., Swiggard, W.J., Steinman, R.M., Bona, C.A., and Zaghouani, H. (1994). Efficient loading of identical peptide onto class II molecules by antigenized immunoglobulin and PR8 virus (in press).Google Scholar
  10. Brumeanu, T.D., Kotanski, T., Bona, C.A., and Zaghouani, H. (1993). A sensitive method to detect defined peptide among those eluted from class II molecules. J. Immun. Methods 160: 65–71.CrossRefGoogle Scholar
  11. Capra, J.D., Tung, A.S., and Nisonoff, A., (1977). Structural studies on induced antibodies with defined idiotype specificities. The complete amino acid sequence of the light chain variable regions of anti-azophenylarsonate antibodies from A/J mice bearing a cross-reactive idiotype. J. Immunol. 119: 993–999.PubMedGoogle Scholar
  12. Carbone, F.R., Bevan, M.J. (1990). Class I-restricted processing and presentation of exogenous cell-associated antigen in vivo. J. Exp. Med. 71: 377–387.CrossRefGoogle Scholar
  13. Chakarbarti, D., Ghosh, S.K. (1992). Induction of syngeneic cytotoxic T lymphocytes against B cell tumors. Cell Immunol. 142: 54–66.CrossRefGoogle Scholar
  14. Chimini, G., Pala, P., Sire, J., Jordan, B.R., and Maryanski, J.L. (1989). Recognition of oligonucleotide-encoded T cell epitopes indtroduce dinto a gene unrelated to the original antigen. J. Exp. Med 169: 297–302.PubMedCrossRefGoogle Scholar
  15. Collins, D.S., Findlay, K., Harding, C.V. (1992). Processing of exogenous liposome-encapsulated antigens in vivo generates class I MHC-restricted T cell responses. J. Immunol. 148: 336–3341.Google Scholar
  16. del Val, M., Hengel, H., Hacker, H., Hartlaub, U., Ruppert, T., Lucin, P., Koszinowski, U.H. (1992). Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medical-Golgi compartment. J. Exp. Med. 176: 729–738.PubMedCrossRefGoogle Scholar
  17. Eichmann, K., and Rajewsky, K. (1975). Induction of T and B cell immunity by anti-idiotypiic antibody. Eur. J. Immunol. 5: 661–666.PubMedCrossRefGoogle Scholar
  18. Ertl, H.C.J. and Bona, C. (1988). Criteria to define anti-idiotypic antibodies carrying the internal image of an antigen. Vaccine 6: 80–84.PubMedCrossRefGoogle Scholar
  19. Falk, K., Rotzschke, O., Deres, K., Metzger, J., Jung, G., and Rammensee, H.G. (1991). Identification of naturally processed viral nonapeptides allows their quantification in infected cells and suggests allele-specific T celll epitope forecast. J. Exp. Med. 174: 425–434.PubMedCrossRefGoogle Scholar
  20. Greenspan, N.S., and Bona, C.A. 1993. Idiotypes: structure and immunogenicity. The FASEB J. 7: 437–444.Google Scholar
  21. Guerder, S., and Matzinger, P. (1992). A fail-safe mechanism for maintaining self tolerance. J. Exp. Med. 176: 553–564.PubMedCrossRefGoogle Scholar
  22. Haberman, A.M., Moller, C., McCreedy, D., Gerhard, W.V. (1990). A large degree of functional diversity exists among helper T cells specific for the same antigenic site of influenza hemagglutinin. J. Immunol. 145: 3087–3094.PubMedGoogle Scholar
  23. Han, Y.S., Braciale, V.L., and Braciale, T.J. (1991). Presentation of viral antigen to class I major histocompatibility complex-restricted cytotoxic T lymphocyte. Recognition of an immunodominant influenza hemagglutinin site by cytotoxic T lymphocyte is independent of the position of the site in the hemagglutinin translation product. J. Exp. Med. 174: 733.CrossRefGoogle Scholar
  24. Infante, A.J., Infante, P.D., Gillis, S., and Fathman, C.G. (1982). Definition of T-cell idiotopes using anti-idiotypic antisera produced by immunization with T-cell clones. J. Exp. Med. 155: 1100–1107.PubMedCrossRefGoogle Scholar
  25. Ito, M., Fredrickson, G.G., Celada, F., Schulman, J.L., Bona, C.A., Moraln, T.M. (1987). Methods for the selection and growth of antigen-specific cytolytic T lines and clones bearing a defined T cell receptor β marker. J. Immunol. Methods 103: 229–237.PubMedCrossRefGoogle Scholar
  26. Jerne, N.K. The immune system: as web of V domains. Harvy Lectures Series 70. Academic Press, New York, San Francisco, London (1976) p 93.Google Scholar
  27. Kaye, J., and Janeway, C.A. (1984). Fab fragement of a directly activating monoclonal antibody that precipitates a disulfide-linked heterodimer from a helper T cell clone blocks activation by either allogeneic Ia or antigen and self-la. J. Exp. Med. 159: 1397–1412.PubMedCrossRefGoogle Scholar
  28. Kisielow, P., Bluthman, H., Staerz, U., Steinmetz, M., von Boehmer, H. (1988). Tolerance in T cell-receptor transgenic involves deletion of nonmature CD4+8+ thymocytes. Nature 333: 742.PubMedCrossRefGoogle Scholar
  29. Kunkel, H.G., Mannick, M., and Williams, R.C. (1963). Individual antigenic specificity of isolated antibodies. Science 140: 1218–1219.PubMedCrossRefGoogle Scholar
  30. Kuzu, Y., Kuzu, H., Zaghouani, H., and Bona, C. Priming of CTL at various stages of ontogeny with tranfectoma cells expressing a chimeric Ig heavy chain gene bearing an influenza virus nucleoprotein peptide. Int. Immunol. (Submitted).Google Scholar
  31. Kuzu, H., Kuzu, Y., Zaghouani, H., and C. Bona, (1993). In vivo priming effect during various stages of ontogeny of an influenza virus nucleoprotein peptide. Eur. J. Immunol.: in press.Google Scholar
  32. Leo, O., Foo, M., Sachs, D.H., Samelson, L.E., and Bluestone, J.A. (1987). Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc. Natl. Acad. Sci. USA 84: 1374.PubMedCrossRefGoogle Scholar
  33. Lindemann, J. (1979) Homobodies: do they exist?. Ann. Immunol. (Inst. Pasteur) 130C, 311–318.Google Scholar
  34. Lopes, L.M., Chain, B.M. (1992). Liposome-mediated delivery stimulates a class I-restriced cytotoxic T cell response to soluble antigen. Eur. J. Immunol. 22: 287–290.PubMedCrossRefGoogle Scholar
  35. Nisonoff, A. and Lamoyi, E. (1981). Implications of the presence of internal image of the antigen in anti-idiotypic antibodies: possible application to vaccine production. Clin. Imm. and Immunopath. 21: 397–406.CrossRefGoogle Scholar
  36. Nonacs, R., Humborg, C., Tarn, J.P. and Steinman, R.M. (1992). Mechanisms of mouse spleen drentritic cell function in the generation of influenza-specific cytoloytic T lymphocytes. J. Exp. Med. 519-529.Google Scholar
  37. Oilier, P., Rocca-Serra, J. Somme, G., Theze, J., and Fougereau, M. 1985. The idiotypic network and the internal image: possible regulation of a germline neetwork by pauci gene encoded Ab2 antibodies in the GAT system, EMBO J. 4: 3681.Google Scholar
  38. Oudin, J. and Michel, M. (1963). Une novelle forme d’allotype des globulines du serum de lapin apparement lie a 1a function et a 1a specificite anticorps. C.R. Acad. Sci, (Paris) 257: 805–808.Google Scholar
  39. Peters, P.J., Neefjes, J.J., Oorschot, V., Ploegh, H.L., Genze, H.J. (1991). Segregation of MHC class II molecules from MCH class I molecules in the Golgi complex for transport to lysosomal compartments. Nature 349: 669–675.PubMedCrossRefGoogle Scholar
  40. Redy, R., Zhou, F., Nair, S., Huang, L., Rouse, B.T. (1992). In vivo cytotoxic T lymphocyte induction with soluble proteins administered in lipsomes. J. of Immunol. 1585-1589.Google Scholar
  41. Rodkey, L.S. (1974). Studies of idiotypic antibodies. Production and characterization of autoanti-idiotypic antisera. J. Exp. Med. 139: 712.PubMedCrossRefGoogle Scholar
  42. Roitt, I.M., Male, D.K., Guarnotta, G., de Carvalho, L.D., Cooke, A., Hay, F.C., Lydyard, P.M., Thanavala, Y., and Ivanyi, J. (1981). Idiotype networks and their possible exploitation for manipulation of the immune response. The Lacet 1: 1041–1045.Google Scholar
  43. Rubinstein, L.J., Yeh, M., and Bona, C.A. (1982). Idiotype-anit-idiotype network II. Activation of silent clones by treatment at birth with idiotopes is associated with the expansion of idiotype-specific helper T cells. J. Exp. Med. 156: 506–521.PubMedCrossRefGoogle Scholar
  44. Rudikoff, S., Pawlita, M., Pumphrey, J., Muskinski, E., and Potter, M. (1983). Galactan antibodies diversity and structure of idiotypes. J. Exp. Med. 158: 1385–1400.PubMedCrossRefGoogle Scholar
  45. Schild, H., Deres, K., Wiesmuller, K.-H, Jung, G., Rammensee, H.-G. (1991). Efficiency of peptides and lipopeptides for in vivo priming of virus specific cytotoxic T cells. Eur. J. Immunol. 2649-2654.Google Scholar
  46. Sitz, L., Schmitz, C., Binder, D., Zinkernagel, R., Paoletti, E., and Becht, H. (1990). Characterization and immunological properties of influenza virus nucleoprotein (NP): cell associated NP isolated from infected cell or viral NP expressed by vaccinia recombinant virus do not confere protection. J. Gen. Virol. 71: 1169.CrossRefGoogle Scholar
  47. Taylor, P.M., Davey, J., Howland, K., Rothbard, J.B., and Askonas, B.A. (1987). Class I MHC molecules rather than other mouse genes dictate influenza epitope recognition by cytotoxic T cell. Immunogenetics 26: 267.PubMedCrossRefGoogle Scholar
  48. Townsend, A.R.M., McMichael, A.J., Carter, N.P., Huddleston, J.A. and Brownlee, G.G. (1984). Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells. Cell 39: 13.PubMedCrossRefGoogle Scholar
  49. Townsend, A.R.M., Rothbard, J., Gotch, F.M., Bahadur, G., Wraith, D., and McMichael, A.J. (1986). The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44: 959–968.PubMedCrossRefGoogle Scholar
  50. Ulmer, J.E., Donnelly, J.J., Parker, S.E., Rhodes, G.H., Feigner, P.L., Dearki, V.J., Gromkowski, S.H., Randall, R.R. Dech, R., DeWitt, C.M., Friedman, A., Hawe, L.A., Leander, K.R., Martinez, D., perry, H.C., Shiver, J.W., Montgomery, D.L., and Liu, M.A. (1993). Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259: 1745.PubMedCrossRefGoogle Scholar
  51. Unanue, E.R. (1989). Macrophages, antigen presenting cells and the phenomenon of antigen handling and presentation in fundamental immunology (W.E. Paul, ed,) Raven Press, N.Y. p.95.Google Scholar
  52. Walters, S.J., Luzzatti, P.R., and Bona, C.A. (1984). Functional properties of T ceil clones with a double specificity for alloantigens and foreign antigens. J. Exp. Med. 160: 1300–1315.CrossRefGoogle Scholar
  53. Waters, S.J., and Bona, C.A. (1988). Characterization of a T cell clone recognizing idiotopes as tumor-associated antigens. Cell. Immunol. 111: 87–93.PubMedCrossRefGoogle Scholar
  54. Zaghouani, H., Krystal, M., Kuzu, H., Moran, T., Shah, H., Kuzu, Y., Schulman, J., Bona, C., (1992). Cells expressing a heavy chain immunoglobulin gene carrying a viral T cell epitope are lysed by specific cytolytic T cells. J. Immunol. 148: 3604–3609.PubMedGoogle Scholar
  55. Zaghouani, H., Steinman, R., Nonacs, R., Shah, H., Gerhard, W. and Bona, C. (1993). Presentation of a viral T cell epitope expressed in the CDR3 region of a self immunoglobulin molecule. Science 1259: 224–227.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Constantin A. Bona
    • 1
  1. 1.Department of MicrobiologyMount Sinai School of MedicineNew YorkUSA

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