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Immune Induction by a Protein Antigen and by a Peptide Segment of the Protein

  • Anne Marie Wan
  • Charles D. Estin
  • Beatrice C. Langton
  • Matthew L. Andria
  • Eli Benjamini
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 185)

Abstract

The immune induction by a protein (the tobacco mosaic virus protein — TMVP) was compared to the immune induction by the free, non-conjugated eicosa tryptic peptide fragment of the protein (tryptic peptide 8 representing residues 93–112 of the protein). The results demonstrated that like TMVP, peptide 8 was immunogenic in A/J mice. TMVP and peptide 8 do not cross react on the T cell level. However, immunization with TMVP or with peptide 8 induces antibodies which react with both TMVP and peptide 8. Characterization of the antibodies produced by both immunogens revealed that: 1) their isotope composition is similar with IgG1 and IgG2 being the predominant isotypes; this composition indicates that both immunogens are T cell dependent antigens, 2) the antibodies induced by TMVP and by peptide 8 are directed against the C-terminal decapeptide portion of peptide 8 (residues 103–112 of the protein), 3) the fine specificity of these antibodies is the same. These results, and results of adoptive transfer experiments, indicate that antigen specific T cells had no effect on the expression of the fine antibody specificity. The results demonstrate the feasibility of immunizing with a portion of a protein for the purpose of inducing antibodies with the same isotype composition and specificity towards a protein epitope as those induced by immunization with the whole protein.

Keywords

Tobacco Mosaic Virus Helper Cell Tryptic Peptide Protein Antigen Fine Specificity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Anderer, F.A. (1963) Preparation and properties of an artificial antigen immunologically related to tobacco mosaic virus. Biochem. Biophys. Acta, 71: 246.PubMedCrossRefGoogle Scholar
  2. Anderer, F.A., and Schlumberger, H.D. (1965) Properties of differ ent artificial antigens immunologically related to tobacco mosaic virus. Biochem. Biophys. Acta, 97: 503.PubMedCrossRefGoogle Scholar
  3. Anderer, F.A., Uhlig, H., Weber, E., and Schramm, G. (1960) Primary structure of the protein of tobacco mosaic virus. Nature, 186: 922.PubMedCrossRefGoogle Scholar
  4. Arnon, R., Maron, E., Sela, M., and Anfinsen, C.B. (1971) Antibodies reactive with lysozyme elicited by a completely synthetic antigen, Proc. Natl. Acad. Sci., 68: 1450.PubMedCrossRefGoogle Scholar
  5. Arnon, R., and Sela, M. (1969) Antibodies to a unique region in lysozyme provoked by a synthetic antigen conjugate. Proc. Natl. Acad. Sci., 62: 163.PubMedCrossRefGoogle Scholar
  6. Atassi, M.Z. (1975) Antigenic structure of myoglobin: the complete immunochemical anatomy of a protein and conclusions relating to antigenic structures of proteins. Immunochemistry, 12: 423.PubMedCrossRefGoogle Scholar
  7. Benjamini, E. (1977) Immunochemistry of the tobacco mosiac virus protein. in: immunochemistry of proteins (M.Z. Atassi, ed.), Plenum Press, New York, 2: 265.CrossRefGoogle Scholar
  8. Benjamini, E., Michaeli, D., Leung, C.Y., Wong, K., and Scheuenstuhl, H. (1973) Immunochemical studies with synthetic peptides related to collagen. Immunochemistry, 10: 629.PubMedCrossRefGoogle Scholar
  9. Benjamini, E., Young, J.D., Shimizu, M., and Leung, C.Y. (1964) Immunochemical studies on the tobacco mosaic virus protein. I. The immunological relationship of the tryptic peptides of the tobacco mosaic virus protein to the whole protein. Biochemistry, 3: 1115.PubMedCrossRefGoogle Scholar
  10. Berzofsky, J. (1983a) T cell activation by antigen: promising clues to receptor genes and molecules. Immunology Today, 4: 299.CrossRefGoogle Scholar
  11. Berzofsky, J.A. (1983b) T-B reciprocity: an Ia-restricted epitope-specific curcuit regulating T cell-B cell interaction and antibody specificity. Surv. Immunol. Res., 2: 223.PubMedGoogle Scholar
  12. Bittle, J.L., Houghten, R.A., Alexander, H., Shinnick, T.M., Sutcliffe, J.G., Lerner, R.A., Rowlands, D.J., and Brown, F. (1982) Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence. Nature, 298: 30.PubMedCrossRefGoogle Scholar
  13. Bixler, G.S., Jr., and Atassi, M.Z. (1983) Molecular localization of the full profile of the continuous regions recognized by myoglobin primed T cells using synthetic overlapping peptides encompassing the entire molecule. Immunological Commun., 12: 593.Google Scholar
  14. Bottomly, K. (1981) Activation of the idiotypic network: environmental and regulatory influences. in: Immunoglobin idiotypes (C.A. Janeway, E.E. Sercarz, H. and Wigzell, eds.), Academic Press, New York, pp. 517.Google Scholar
  15. Brown, R.K., Delaney, R., Levine, L., and van Vanakis, H. (1959) Studies on the antigenic structure of ribonuclease. J. Biol. Chem., 2334: 2343.Google Scholar
  16. Cecka, J.M., Stratton, J.A., Miller, A. and Sercarz, E. (1976) Structural aspects of immune recognition of lysozyme. III. T cell specificity restriction and its consequences for antibody antibody specificity. Eur. J. Immunol., 6: 639.PubMedCrossRefGoogle Scholar
  17. Champness, J.N., Bloomer, A.C., Bricogne, G., Butler, P.J.G., and Klug, A. (1976) The structure of the protein disc of the tobacco mosaic virus to 5 A resolution. Nature, Lond., 259: 20.CrossRefGoogle Scholar
  18. Chavez, L.G., and Scheraga, H.H. (1979) Location of antigenic determinants of bovine pancreatic ribonuclease. Biochemistry, 18: 4386.PubMedCrossRefGoogle Scholar
  19. Corradin, G., Etlinger, H.N., and Chiller, J.M. (1977) Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice. J. Immunol., 119: 1048.PubMedGoogle Scholar
  20. Crumpton, M.J., and Sonali, P.A. Jr. (1967) Conformation of immunologically active fragments of sperm whale myoglobin in solution. J. Mol. Biol., 26: 143.PubMedCrossRefGoogle Scholar
  21. Fearney, F.J., Leung, C.Y., Young, J.D., and Benjamini, E. (1971) The specificity of antibodies to a peptide determinant of the tobacco mosaic virus proeinm induced by immunization with the peptide conjugate. Biochim. Biophys. Acta, 243–509.Google Scholar
  22. Gerwing, J., and Thompson, K. (1968) Studies on antigenic properties of eggwhite lysozyme. I. Isolation and characterization of a tryptic peptide from reduced and alkylated lysozyme exhibiting hapten activity. Biochemistry, 7: 3888.PubMedCrossRefGoogle Scholar
  23. Goodfried, T.L., Levine, L., and Fasman, G.D. (1964) Antibodies to bradykinin and angiotensin: a use of a carbodiimide in immunology. Science, 14: 1344.CrossRefGoogle Scholar
  24. Green, N., Alexander, H., Olson, A., Alexander, S., Shinnick, T.M., Sutcliffe, J.B., and Lerner, R.A. (1982) Immunogenic structure of the influenza virus hemagglutinin. Cell, 28: 477.PubMedCrossRefGoogle Scholar
  25. Hamaoka, T., Katz, D.H., and Benaceraf, B. (1972) Radio-resistance of carrier-specific helper thymus-derived lymphocytes in mice. Proc. Natl. Acad. Sci., (U.S.A.) 69: 3453.CrossRefGoogle Scholar
  26. Hashim, G.A. (1978) Myelin basic protein: structure function and antigenic determinants. Immunol. Review, 39: 60.CrossRefGoogle Scholar
  27. Burrell, J.G.R., Smith, J.A., and Leach, S.J. (1978) The detection of five antigenically reactive regions in the soybean leghemoglobin “a” molecule. Immunochemistry, 15: 297.CrossRefGoogle Scholar
  28. Janeway, C.A. Jr., Murgita, R.A., Weinbaum, F.I., Asofsky, R., and Wigzell, H. (1977) Evidence for an immunoglobulin-dependent antigen-specific helper cell. Proc. Natl. Acad. Sci., 74: 4582.PubMedCrossRefGoogle Scholar
  29. Kaattari, S., Scibienski, R.J., and Benjamini, E. (1980) The immunoregulatory role of antigen-antibody complexes. Immunology, 40: 9.PubMedGoogle Scholar
  30. Kettman, J.R., Benjamini, E., Michaeli, D., and Leung, C.Y., (1967) The synthesis and immunological activity of a peptide related to collagen, Biochem. Biophys. Res. Commun., 29: 623.PubMedCrossRefGoogle Scholar
  31. Langbeheim, H.N., Arnoon, R., and Sela, M. (1976) Antiviral effect on MS-2 coliophage obtained from a synthetic antigen. Proc. Natl. Acad. Sci., 73: 4636.PubMedCrossRefGoogle Scholar
  32. Lerner, R.A. (1982) Tapping the immunological repertoire to produce antibodies of predetermined specificity. Nature, 299: 592.CrossRefGoogle Scholar
  33. Mishell, B.B., and Shiigi, S.M. (1980) “Selected Methods in Cellular Immunology,” W.H. Freeman and Co., San Francisco.Google Scholar
  34. Mitchison, N.A. (1971) The carrier effect in the secondary response to hapten protein conjugates II: Cell cooperation. Eur. J. Immunology, 1: 18.CrossRefGoogle Scholar
  35. Morrow, P.R., Rennick, D.M., and Benjamini, E. (1983) The antibody response to a single antigenic determinant of the tobacco mosaic virus protein (TMVP): effects of allotype-linked genes and restricted heterogeneity of the response. J. Immunol. 131: 2875.PubMedGoogle Scholar
  36. Muller, G.M., Shapira, M., and Arnon, R. (1982) Anti-influenza response achieved by immunization with a synthetic conjugate. Proc. Natl. Acad. Sci., 79: 569.PubMedCrossRefGoogle Scholar
  37. Prince, A.M., Ikram, H.I., and Hopp, T.P. (1982) Hepatitis B virus vaccine: identification of HBsAg/a and HBsAg/d but not HBsAg/y subtype antigenic determinants on a synthetic immunogenic peptide, Proc. Natl. Acad. Sci., 79: 579.PubMedCrossRefGoogle Scholar
  38. Rennick, D.M., Morrow, P.R., and Benjamini, E. (1983) Functional heterogeneity of memory B lymphocytes: in vivo analysis of TD-primed B cells responsive to secondary stimulation with TD and TI antigens. J. Immunol., 131: 561.PubMedGoogle Scholar
  39. Sakata, S., and Atassi, M.Z. (1980) Immunochemistry of serum albumin. X. Five major antigenic sites of human serum albumin are extrapolated from bovine albumin and confirmed by synthetic peptides Molecular, Immunology., 17: 139.Google Scholar
  40. Salvin, S.B., and Smith, R.G. (1960) Delayed hypersensitivity and an anmnastic response. J. Immunol., 84: 44.Google Scholar
  41. Schechter, B., Schechter, I., Ramachandran, J., Conway-Jacobs, A., Sela, M., Benjamini, E., and Shimizu, M. (1971) Synthetic containing the same L-tyrosyl-alanyl-L-glutamyl sequences. Eur. J. Biochem., 20: 309.PubMedCrossRefGoogle Scholar
  42. Scibienski, R.J., Klingman, V., Leung, C., Thompson, K., and Benjamini, E. (1978) Recognition of lysozyme by lymphocyte subunits. in: Immunobiology of Proteins and Peptides 1 (M.Z. Medicine and Biology 98: 305.Google Scholar
  43. Sela, M. (1969) Antigenicity: some molecular aspects. Science., 166: 1365.PubMedCrossRefGoogle Scholar
  44. Senyk, G., Williams, E.B., Nitecki, D.E., and Goodman, J.W. (1983) The functional dissection of an antigen molecule: specificity of humoral and cellular immune responses to glucagons, J. Exp. Med., 133: 1294.CrossRefGoogle Scholar
  45. Sercarz, E., Cecka, J.M., Kipp, D., and Miller, A. (1977) The steering function of T cells in expression of the antibody repertoire directed against multideterminant protein antigen. Ann. Immunol., Paris. 128c: 599.Google Scholar
  46. Sercarz, E., Wicher, L., Stratton, J., Miller, A., Metzyer, D., Maizel, R., Katz, M., Harvey, M., and Benjamini, C. (1981) Regulation of antibody specificity and idiotypy by independent T cells. in: Immunoglobin Idiotypes ( C.A. Janeway, E.E. Sercarz, H. Wigzell, eds.) Acad. Press, New York, pp. 533.Google Scholar
  47. Spitler, L., Benjamini, E. Young, J.D., Kaplan, H., and Fudenberg, H H. (1970) Studies on the immune response to a characterized antigen determinant of the tobacco mosaic virus protein. J. Exp. Med.,, 131: 133.Google Scholar
  48. Tsugita, A., Gish, D.T., HYoung, J. Fraenkel-Conrat, H., Knight, C.A., and Stanley, W.M. (1960) The complete amino acid sequence of the protein of the tobacco mosaic virus. Proc. Natl. Acad. Sci., 46: 1460.Google Scholar
  49. Woody, B,.R., and Knight, C.A. (1959) Peptide maps obtained with tryptic digests of the proteins of some strains of tobacco mosaic virus. Virology, 9: 359.PubMedCrossRefGoogle Scholar
  50. Young, C.R., and Atassi, M.Z. (1982) Antibodies to sperm-whale myoglobin evoked by free synthetic peptides fo an antigenic site. Immunological Communications 11: 9.PubMedGoogle Scholar
  51. Young, J.D., Benjamini, E., Stewart, J.M., and Leung, C.Y. (1967) Immunochemical studies on the tobacco mosaic virus protein. V. The solid phase synthesis of peptides of an antigenically active decapeptide of tobacco mosaic virus protein and the reaction of these peptides with antibodies to the whole protein. Biochemistry, 6: 1455.PubMedCrossRefGoogle Scholar
  52. Waterfield, D., Levy, J.G., Kilburn, D.G. and Teather, R.M. (1972) The effect of haptenic peptides from performic acid oxidized ferredoxin from Clostridium pasteurionium and protein carrier-hapten conjugates on the immune response of macrophages and lymphoid cells from animals immunized against oxidized ferredoxin. Cell. Immunol., 113: 58.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Anne Marie Wan
    • 1
  • Charles D. Estin
    • 1
  • Beatrice C. Langton
    • 1
  • Matthew L. Andria
    • 1
  • Eli Benjamini
    • 1
  1. 1.Department of Medical Microbiology and Immunology School of MedicineUniversity of CaliforniaDavisUSA

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