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. 1987 Sep 1;166(3):693–701. doi: 10.1084/jem.166.3.693

Mouse H-2k-restricted cytotoxic T cells recognize antigenic determinants in both the HA1 and HA2 subunits of the influenza A/PR/8/34 hemagglutinin

PMCID: PMC2188694  PMID: 2442286

Abstract

We have constructed two chimeric influenza hemagglutinin (HA) genes in which the HA1 and HA2 subunits of the HA molecule have been interchanged between influenza A/PR/8/34 (H1 subtype) and A/NT/60/68 (H3 subtype). These genes were used to construct recombinant vaccinia viruses that expressed intact chimeric HA. These recombinant viruses were used to test whether murine CTL recognize antigenic determinants in either the HA1, HA2, or both subunits. We found that both subunits of the HA molecule contain determinants for CTL. This implies that CTL have, at least in part, separate antigenic determinants from B lymphocytes, which recognize mainly epitopes within the HA1 subunit.

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Selected References

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  1. Andrew M. E., Coupar B. E., Ada G. L., Boyle D. B. Cell-mediated immune responses to influenza virus antigens expressed by vaccinia virus recombinants. Microb Pathog. 1986 Oct;1(5):443–452. doi: 10.1016/0882-4010(86)90006-9. [DOI] [PubMed] [Google Scholar]
  2. Becht H., Huang R. T., Fleischer B., Boschek C. B., Rott R. Immunogenic properties of the small chain HA2 of the haemagglutinin of influenza viruses. J Gen Virol. 1984 Jan;65(Pt 1):173–183. doi: 10.1099/0022-1317-65-1-173. [DOI] [PubMed] [Google Scholar]
  3. Bennink J. R., Yewdell J. W., Smith G. L., Moller C., Moss B. Recombinant vaccinia virus primes and stimulates influenza haemagglutinin-specific cytotoxic T cells. Nature. 1984 Oct 11;311(5986):578–579. doi: 10.1038/311578a0. [DOI] [PubMed] [Google Scholar]
  4. Bennink J. R., Yewdell J. W., Smith G. L., Moss B. Recognition of cloned influenza virus hemagglutinin gene products by cytotoxic T lymphocytes. J Virol. 1986 Mar;57(3):786–791. doi: 10.1128/jvi.57.3.786-791.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Both G. W., Sleigh M. J. Complete nucleotide sequence of the haemagglutinin gene from a human influenza virus of the Hong Kong subtype. Nucleic Acids Res. 1980 Jun 25;8(12):2561–2575. doi: 10.1093/nar/8.12.2561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Braciale T. J., Braciale V. L., Henkel T. J., Sambrook J., Gething M. J. Cytotoxic T lymphocyte recognition of the influenza hemagglutinin gene product expressed by DNA-mediated gene transfer. J Exp Med. 1984 Feb 1;159(2):341–354. doi: 10.1084/jem.159.2.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Braciale T. J., Henkel T. J., Lukacher A., Braciale V. L. Fine specificity and antigen receptor expression among influenza virus-specific cytolytic T lymphocyte clones. J Immunol. 1986 Aug 1;137(3):995–1002. [PubMed] [Google Scholar]
  8. Caton A. J., Brownlee G. G., Yewdell J. W., Gerhard W. The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell. 1982 Dec;31(2 Pt 1):417–427. doi: 10.1016/0092-8674(82)90135-0. [DOI] [PubMed] [Google Scholar]
  9. Cranage M. P., Kouzarides T., Bankier A. T., Satchwell S., Weston K., Tomlinson P., Barrell B., Hart H., Bell S. E., Minson A. C. Identification of the human cytomegalovirus glycoprotein B gene and induction of neutralizing antibodies via its expression in recombinant vaccinia virus. EMBO J. 1986 Nov;5(11):3057–3063. doi: 10.1002/j.1460-2075.1986.tb04606.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DeLisi C., Berzofsky J. A. T-cell antigenic sites tend to be amphipathic structures. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7048–7052. doi: 10.1073/pnas.82.20.7048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hurwitz J. L., Herber-Katz E., Hackett C. J., Gerhard W. Characterization of the murine TH response to influenza virus hemagglutinin: evidence for three major specificities. J Immunol. 1984 Dec;133(6):3371–3377. [PubMed] [Google Scholar]
  12. Katz J. M., Laver W. G., White D. O., Anders E. M. Recognition of influenza virus hemagglutinin by subtype-specific and cross-reactive proliferative T cells: contribution of HA1 and HA2 polypeptide chains. J Immunol. 1985 Jan;134(1):616–622. [PubMed] [Google Scholar]
  13. Mackett M., Smith G. L., Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. J Virol. 1984 Mar;49(3):857–864. doi: 10.1128/jvi.49.3.857-864.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maryanski J. L., Pala P., Corradin G., Jordan B. R., Cerottini J. C. H-2-restricted cytolytic T cells specific for HLA can recognize a synthetic HLA peptide. Nature. 1986 Dec 11;324(6097):578–579. doi: 10.1038/324578a0. [DOI] [PubMed] [Google Scholar]
  15. McMichael A. J., Gotch F. M., Noble G. R., Beare P. A. Cytotoxic T-cell immunity to influenza. N Engl J Med. 1983 Jul 7;309(1):13–17. doi: 10.1056/NEJM198307073090103. [DOI] [PubMed] [Google Scholar]
  16. Townsend A. R., Bastin J., Gould K., Brownlee G. G. Cytotoxic T lymphocytes recognize influenza haemagglutinin that lacks a signal sequence. Nature. 1986 Dec 11;324(6097):575–577. doi: 10.1038/324575a0. [DOI] [PubMed] [Google Scholar]
  17. Townsend A. R., Gotch F. M., Davey J. Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell. 1985 Sep;42(2):457–467. doi: 10.1016/0092-8674(85)90103-5. [DOI] [PubMed] [Google Scholar]
  18. Townsend A. R., McMichael A. J., Carter N. P., Huddleston J. A., Brownlee G. G. Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells. Cell. 1984 Nov;39(1):13–25. doi: 10.1016/0092-8674(84)90187-9. [DOI] [PubMed] [Google Scholar]
  19. Townsend A. R., McMichael A. J. Specificity of cytotoxic T lymphocytes stimulated with influenza virus. Studies in mice and humans. Prog Allergy. 1985;36:10–43. doi: 10.1159/000409860. [DOI] [PubMed] [Google Scholar]
  20. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  21. Wabuke-Bunoti M. A., Fan D. P., Braciale T. J. Stimulation of anti-influenza cytolytic T lymphocytes by CNBr cleavage fragments of the viral hemagglutinin. J Immunol. 1981 Sep;127(3):1122–1125. [PubMed] [Google Scholar]
  22. Wabuke-Bunoti M. A., Fan D. P. Isolation and characterization of a CNBr cleavage peptide of influenza viral hemagglutinin stimulatory for mouse cytolytic T lymphocytes. J Immunol. 1983 May;130(5):2386–2391. [PubMed] [Google Scholar]
  23. Wabuke-Bunoti M. A., Taku A., Fan D. P., Kent S., Webster R. G. Cytolytic T lymphocyte and antibody responses to synthetic peptides of influenza virus hemagglutinin. J Immunol. 1984 Oct;133(4):2194–2201. [PubMed] [Google Scholar]
  24. Ward C. W. Structure of the influenza virus hemagglutinin. Curr Top Microbiol Immunol. 1981;94-95:1–74. doi: 10.1007/978-3-642-68120-2_1. [DOI] [PubMed] [Google Scholar]
  25. Wiley D. C., Wilson I. A., Skehel J. J. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature. 1981 Jan 29;289(5796):373–378. doi: 10.1038/289373a0. [DOI] [PubMed] [Google Scholar]
  26. Yamada A., Young J. F., Ennis F. A. Influenza virus subtype-specific cytotoxic T lymphocytes lyse target cells coated with a protein produced in E. coli. J Exp Med. 1985 Nov 1;162(5):1720–1725. doi: 10.1084/jem.162.5.1720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yamada A., Ziese M. R., Young J. F., Yamada Y. K., Ennis F. A. Influenza virus hemagglutinin-specific cytotoxic T cell response induced by polypeptide produced in Escherichia coli. J Exp Med. 1985 Aug 1;162(2):663–674. doi: 10.1084/jem.162.2.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yap K. L., Ada G. L., McKenzie I. F. Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature. 1978 May 18;273(5659):238–239. doi: 10.1038/273238a0. [DOI] [PubMed] [Google Scholar]
  29. Yewdell J. W., Bennink J. R., Smith G. L., Moss B. Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1785–1789. doi: 10.1073/pnas.82.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ziegler H. K., Unanue E. R. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci U S A. 1982 Jan;79(1):175–178. doi: 10.1073/pnas.79.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]
  32. Zoller M. J., Smith M. Oligonucleotide-directed mutagenesis using M13-derived vectors: an efficient and general procedure for the production of point mutations in any fragment of DNA. Nucleic Acids Res. 1982 Oct 25;10(20):6487–6500. doi: 10.1093/nar/10.20.6487. [DOI] [PMC free article] [PubMed] [Google Scholar]

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