Cytotoxic and Helper T-Lymphocyte Responses to Antibody Recognition Regions on Influenza Virus Hemagglutinin

  • M. Zouhair Atassi
  • Jose V. Torres
  • Philip R. Wyde

Abstract

We have previously localized and synthesized twelve antibody recognition sites on influenza virus hemaggl uti ni n (HA). These peptides correspond to exposed surface areas in the 3-D structure of HA. Using intact X31 virus as the i mmnunogen, we have determined the recognition of these synthetic peptides by proliferative T-helper lymphocytes (ThL) , delayed type hypersensitivity (DTH) , and cytotoxic T-lymphocytes (CTL) responses. The responses to the individual determinants in each of these immune compartments were under separate Ir gene control. Conversely, using the peptides as immunogens, we have determined the ability of various peptide-specific antibodies (in outbred mice) and ThLs (in H-2k, H-2d, H-2s and H-2b mice) to recognize intact virus. Whereas most of the peptides primed the mice for an anti-peptide proliferative ThL response, only very few of these cross-reacted wi th the virus. The identity of the peptide(s) eliciting virus cross-reactive ThLs varied with the strain. The importance of antibody, ThL, CTL and DTH responses in protection against viral infection and in vaccine design is discussed.

Keywords

Influenza Virus Tobacco Mosaic Virus Delay Type Hypersensitivity Antigenic Site Antigenic Structure 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anderer, F.A. (1963) Preparation and properties of an artificial antigen immunologically related to tobacco mosaic virus. Biochim. Biophys. Acta 71:246–248.PubMedCrossRefGoogle Scholar
  2. Anderer, F.A. and Schlumberger, H.D. (1965) Properties of different artificial antigens immunologically related to tobacco mosaic virus. Bi ochi m. Biophys. Acta 97:503–509.CrossRefGoogle Scholar
  3. Andrew, M.E., Braciale, V.L., Henkel, T.J., Hatch, J.A. and Braciale, T.J. (1985) Stable expression of cytolytic activity by influenza virusspecific cytotoxic T lymphocytes. J. Immunol. 135:3520–3525.PubMedGoogle Scholar
  4. Arnon, R., Ed) (1987) “Synthetic Vaccines”, I, pp. 1–155 and Volume II, pp. 1–161, CRC Press, Inc., Boca Raton, Fl.Google Scholar
  5. Atassi, M. Z. (1975) Antigenic structure of myogl o bi n. The complete i mmunochemi cal anatomy of a protein and conclusions relating to antigenic structure of proteins. Immunochem. 12:423–438.CrossRefGoogle Scholar
  6. Atassi, M.Z. (1978) Precise determination of the entire antigenic structure of lysozyme: Molecular features of protein antigenic structures and potential of ,surface-stimulation, synthesis: A powerful new concept for protein binding sites. Immunochem. 15:909–936.CrossRefGoogle Scholar
  7. Atassi, M.Z. (1981) Investigation by synthesis whether antigenic sites of polymeric cytochromne coincide with locations of sequence differences between the immunizing and host cytochromes. Mol. Immunol. 18:1021–1025.PubMedCrossRefGoogle Scholar
  8. Atassi, M.Z. (1982) Immune recognition of serum albumin. 15. Localization by synthetic of antigenic site 4 of bovine serum albumin to the region around the disulfide bond 166–176. Biochim. Biophys. Acta 704:552–555.PubMedCrossRefGoogle Scholar
  9. Atassi, M.Z. (1984) Antigenic structures of proteins. Their determination has revealed important aspects of immune recognition and generated strategies for synthetic mimicking of protein binding sites. Europ. J. Biochem. 145:1–20.PubMedCrossRefGoogle Scholar
  10. Atassi, M.Z. (1985) in: “High Technology Route to Virus Vaccines”, G. Dreesman and R. Kennedy, eds., pp. 17–29, Amer. Soc. Microbiol., Washington, D.C.Google Scholar
  11. Atassi, M.Z. and Bixler, G.S. (1988) in: “Vaccines: New Concepts and Developments” (H. Kohler and P.T. LoVerde, eds., pp. 58–70, Longman Scientific and Technical, Harlow, England.Google Scholar
  12. Atassi, M.L. and Kazim, A.L. (1978) First Consequences of the determination of the entire antigenic structure of sperm-whale myogl obin. Adv. Exptl. Med. Biol. 98:19–40.CrossRefGoogle Scholar
  13. Atassi, M.Z. and Kurisaki, J.I. (1984) A novel approach for localization of the continuous protein antigenic sites by comprehensive synthetic surface scanning: Antibody and T-cell activity to several influenza hemagglutinin synthetic sites. Immunol. Comn. 13:539–551.Google Scholar
  14. Atassi, M.Z. and Kurisaki, J.I. (1986) Synthetic localization of T- and B-cell recognition sites of influenza virus hemagglutinin and the antibody of the T-cell responses to the sites. Protides Biol. Fluids 34:157–160.Google Scholar
  15. Atassi, M.Z. and Webster, R.G. (1983) Localization, synthesis and activity of an antigenic site on influenza virus hemagglutinin. Proc. Natl. Acad. Sci. USA 80:840–844.PubMedCrossRefGoogle Scholar
  16. Atassi, M.Z., Sakata, S. and Kazim, A.L. (1979) Localization and verification by synthesis of five antigenic sites of bovine serum albumin. Biochem J 179: 327–331PubMedGoogle Scholar
  17. Benjamini, E. (1977) in: “Immunochemistry of Proteins”, M.Z. Atassi, ed., pp. 265–310, Plenum Press, New York.CrossRefGoogle Scholar
  18. Benjamini, E., Michaeli, D. and Young, J.D. (1972) Antigenic determinants of proteins of defined sequences. Curr. Top. Microbiol. Immunol. 58:85–134.PubMedCrossRefGoogle Scholar
  19. Bixler, G.S. and Atassi, M.Z. (1983) Molecular localization of the full profile of the continuous regions recognized by myogl obi n primed T-cells using synthetic overlapping peptides encompassing the entire molecule. Immunol. Commun. 12:593–603.PubMedGoogle Scholar
  20. Bbixler, G.S. and Atassi, M.Z. (1984) T-cell recognition of mnyogl obi n. Localization of the sites stimulating T-cell proliferative responses by synthetic overlapping peptides encompassing the entire molecule. J. Immunogenet. 11:339–353.CrossRefGoogle Scholar
  21. Bixler, G.S., Yoshida, T. and Atassi, M.Z., (1984a) T-cell recognition of lysozyme. I. Localization of regions stimulating T-cell proliferative responses by synthetic overlapping peptides encompassing the entire molecule. Expl. Clin. Immunogen 1:99–111.Google Scholar
  22. Bixler, G.S., Yoshida, T. and Atassi, M.Z. (1984b) Localization and genetic control of the continuous T-cell recognition sites of lysozyme by synthetic overlapping peptides representing the full profile of the protein chain. J. Immunogenet. 11:327–338.PubMedCrossRefGoogle Scholar
  23. Bosch, F., Orlich, M., Kilenk, H.D. and Rott, R. (1979) The structure of the hemagglutinin, a determinant for the pathogenicity of influenza viruses. Virol. 95:197–201.CrossRefGoogle Scholar
  24. Braciale, T.J.J. (1979) Specificity of cytotoxic T cells directed to influenza virus hemagglutinin. J. Exp. Med. 149:856–868.PubMedCrossRefGoogle Scholar
  25. Caton, A.J., Yewdell, G.G., Brownlee, J.W. and Gerhard, W. (1982) The antigenic structure of the influenza virus hemagglutinin (H1 subtype). Cell 31:417–422.PubMedCrossRefGoogle Scholar
  26. Fearny, 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 protein induced by immunization with the peptide conjugate. Biochim. Biophys. Acta 243:509–514.CrossRefGoogle Scholar
  27. Kazim, A.L. and Atassi, M.Z. (1980) A novel and comprehensive synthetic approach for the elucidation of protein antigenic structures: Determination of the full antigenic profile of the alpha chain of human hemoglobin. Biochem. J. 191:261–264.PubMedGoogle Scholar
  28. Kazimn, A.L. and Atassi, M.Z. (1982) Structurally inherent antigenic sites. Localization of the antigenic sites of the alpha chain of human hemoglobin in three host species by comprehensive synthetic approach. Biochem. J. 203:201–208.Google Scholar
  29. Klenk, H.D. and Garten, W., Keil, W., Niemann, H., Bosch, F. X., Schwarz, R. T., Scholtissek, C. and Rott, R. (1981) Processing of the Hemagglutinin in: “Genetic Variation Among Influenza Viruses” D.P. Nayak, ed., pp. 193, Academic Press, San Francisco, CA.Google Scholar
  30. Kohler, H. and Loverde, P.T. (1988) “Vaccines, New Concepts and Developments” John Wiley and Sons, New York, N.Y.Google Scholar
  31. Krco, C.J., Abramson, E.J., Atassi, M.Z. and David, C.S. (1984) Genetic control of the immune response to haemoglobin. V. Production and characterization of as restricted T cell lines and clones. J. Immunogenet. 11:33–43.PubMedCrossRefGoogle Scholar
  32. Krco, C.J., Kazim, A.L., Atassi, M.Z. and David, C.S. (1981a) Genetic control of the immune response to hemoglobin. I. Separate genetic control of the α- and β-subunits of human hemoglobin and the influence of the H-2D end by in vitro lymphocyte proliferative response. J. Immunogenet. 8:315–322.PubMedCrossRefGoogle Scholar
  33. Krco, C.J., Kazim, A.L., Atassi, M.Z. and David, C.S. (1981b) Genetic control of the immune response to haemoglobin. III. Variants but not Ac (D2.GD) Ia polypeptides alter T-cell immune responsiveness towards the a-subunit of human haemoglobin. J. Immunoaenet. 8:471–476.CrossRefGoogle Scholar
  34. Lazarowitz, S.G. and Choppin, P.W. (1975) Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin pol vpepti de. Virol. 68:440–445.CrossRefGoogle Scholar
  35. Morrison, L.A., Lukacher, A.E., Braciale, V.L., Fan, D.P. and Braciale, T.J.(1986) Differences in antigen presentation to MHC class I- and class II-restricted influenza virus-specific cytotoxic T lymphocyte clones. J. Exp. Med. 163:903–911.PubMedCrossRefGoogle Scholar
  36. Okuda, K., Twining, S.S., David, C.S. and Atassi, M.Z. (1979) Genetic control of the immune response to sperm-whale myoglobin in mice. II. T-lymphocyte proliferative response to the synthetic antigenic sites. J. Immunol. 123:182–188.PubMedGoogle Scholar
  37. Potter, C.W. and Oxford, J.S. (1979) Determinants of immunity to influenza infection in man. Br. Med. Bull. 35:69–73.PubMedGoogle Scholar
  38. Rott, R. (1979) Molecular basis of infectivity and pathogenicity of mvxovirus. Arch. Virol. 59:285–290.PubMedCrossRefGoogle Scholar
  39. Skehel, J.J. (1972) Polypepti de synthesis in influenza virus-infected cP11c. Virnl. 49:23–28.Google Scholar
  40. Skehel, J.J and Schild, G.C. (1971) The polypeptide composition of influenza A viruses. Virol. 44:396–401.CrossRefGoogle Scholar
  41. Torres, J.V., Wyde, P.R. and Atassi, M.Z. (1988) Cytotoxic Tlymphocytes recognition sites on influenza virus hemagglutinin. Immunol. Letters 19:49–54.CrossRefGoogle Scholar
  42. 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 Lcells. Cell 39:13–17.CrossRefGoogle Scholar
  43. Wabuke-Buenotf, M.A.N., Taku, A., Fan, D.P., Kent, S. and Webster, R.G.(1984) Cytolytic T lymphocytes and antibody responses to synthetic peptides of influenza virus hemagglutinin. J. Immunol. 133:2194–2201.Google Scholar
  44. Ward, C.W. (1981) Structure of influenza virus hemagglutinin. Curr. Top. Imnunol. Microbiol. 94:1–9.CrossRefGoogle Scholar
  45. Webster, R.G., Laver, W.G., Mair, G. and Schild, G.C. (1982) Molecular mechanisms of variation in influenza viruses. Nature 296:115–118.PubMedCrossRefGoogle Scholar
  46. White, J., Kartenbeck, J.S. and Helenius, A. (1982) Tlembrane Fusion Activity of Influenzd Virus. EMBO J. 1:217–222.PubMedGoogle Scholar
  47. Wiley, D.C., Skehel, J.J. and Waterfield, M.D.(1977) Evidence from studies with a cross-linking reagent that the haemagglutinin of influenza virus is a trimer. Virol. 79:446–451.CrossRefGoogle Scholar
  48. Wiley, D.C., Wilson, I.A. and Skehel, J.J. (1981) Structural identification of the antibody-binding sites of Hong Kong influenza hemagglutinin and their involvement in antigenic variation. Nature 289:373–378.PubMedCrossRefGoogle Scholar
  49. Yewdell, J.W., Webster, R.G. and Gerhard, W.U. (1979) Antigenic variation in three distinct determinants of an influenza type A haemagglutinin molecule. Nature 279:246–250.PubMedCrossRefGoogle Scholar
  50. Yoshioka, N. and Atassi, M.Z. (1986) T-cell recognition of human haemoglobin: Localization of the full T-cell recognition profile of the beta chain by a comprehensive synthetic strategy. Biochem. J. 234:457–461.PubMedGoogle Scholar
  51. Young, C.R. and Atassi, M.Z. (1982) Dissection of the molecular parameters for T cell recognition of a myogl obin antigenic site. Adv. Exp. Med. 150:79–93.Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • M. Zouhair Atassi
    • 1
    • 2
  • Jose V. Torres
    • 2
  • Philip R. Wyde
    • 2
  1. 1.Department of BiochemistryBaylor College of MedicineHoustonUSA
  2. 2.Department of Microbiology/ ImmunologyBaylor College of MedicineHoustonUSA

Personalised recommendations