Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1980 Apr 1;151(4):945–958. doi: 10.1084/jem.151.4.945

Recognition of viral glycoproteins by influenza A-specific cross- reactive cytolytic T lymphocytes

PMCID: PMC2185822  PMID: 6154763

Abstract

Two populations of cytolytic T lymphocytes (CTL) generated after influenza A virus infection can be distinguished into one with specificity for the sensitizing hemagglutinin type and a second with cross-reactivity for antigens induced by other type-A influenza viruses. The molecules carrying the antigenic determinants recognized by the cross-reactive CTL were studied. In L-929 cells abortively infected with fowl plague virus, matrix (M) protein synthesis is specifically inhibited, whereas the envelope glycoproteins, hemagglutinin and neuraminidase, are synthesized and incorporated into the plasma membrane. These target cells were lysed by cross-reactive CTL. The envelope proteins of type A/Victoria virus were separated from the other virion components and reconstituted into lipid vesicles that lacked M protein that subsequently were used to prepare artificial target cells. Target-cell formation with vesicles was achieved by addition of fusion-active Sendai virus. These artificial target cells were also susceptible to lysis by cross-reactive CTL. In contrast to previous observations that suggested that the M protein of influenza viruses is recognized by these effector cells, we present evidence that the antigencic determinants induced by the viral glycoproteins are recognized.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ada G. L., Yap K. L. The measurement of haemagglutinin and matrix protein present on the surface of influenza virus infected P815 mastocytoma cells. J Gen Virol. 1979 Mar;42(3):541–553. doi: 10.1099/0022-1317-42-3-541. [DOI] [PubMed] [Google Scholar]
  2. Biddison W. E., Doherty P. C., Webster R. G. Antibody to influenza virus matrix protein detects a common antigen on the surface of cells infected with type A influenza viruses. J Exp Med. 1977 Sep 1;146(3):690–697. doi: 10.1084/jem.146.3.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Braciale T. J. Immunologic recognition of influenza virus-infected cells. I. Generation of a virus-strain specific and a cross-reactive subpopulation of cytotoxic T cells in the response to type A influenza viruses of different subtypes. Cell Immunol. 1977 Oct;33(2):423–436. doi: 10.1016/0008-8749(77)90170-8. [DOI] [PubMed] [Google Scholar]
  4. Braciale T. J. Immunologic recognition of influenza virus-infected cells. II. Expression of influenza A matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic T cells. J Exp Med. 1977 Sep 1;146(3):673–689. doi: 10.1084/jem.146.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Braciale T. J. Specificity of cytotoxicity T cells directed to influenza virus hemagglutinin. J Exp Med. 1979 Apr 1;149(4):856–869. doi: 10.1084/jem.149.4.856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Braciale T. J., Yap K. L. Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells. J Exp Med. 1978 Apr 1;147(4):1236–1252. doi: 10.1084/jem.147.4.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cancro M. P., Gerhard W., Klinman N. R. The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice. J Exp Med. 1978 Mar 1;147(3):776–787. doi: 10.1084/jem.147.3.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Critchley D. R. Cell surface proteins of NIL1 hamster fibroblasts labeled by a galactose oxidase, tritiated borohydride method. Cell. 1974 Oct;3(2):121–125. doi: 10.1016/0092-8674(74)90115-9. [DOI] [PubMed] [Google Scholar]
  9. Doherty P. C., Effros R. B., Bennink J. Heterogeneity of the cytotoxic response of thymus-derived lymphocytes after immunization with influenza viruses. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1209–1213. doi: 10.1073/pnas.74.3.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Effros R. B., Bennink J., Doherty P. C. Characteristics of secondary cytotoxic T-cell responses in mice infected with influenza A viruses. Cell Immunol. 1978 Mar 15;36(2):345–353. doi: 10.1016/0008-8749(78)90278-2. [DOI] [PubMed] [Google Scholar]
  11. Effros R. B., Doherty P. C., Gerhard W., Bennink J. Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses. J Exp Med. 1977 Mar 1;145(3):557–568. doi: 10.1084/jem.145.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ennis F. A., Martin W. J., Verbonitz M. W., Butchko G. M. Specificity studies on cytotoxic thymus-derived lymphocytes reactive with influenza virus-infected cells: evidence for dual recognition of H-2 and viral hemagglutinin antigens. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3006–3010. doi: 10.1073/pnas.74.7.3006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ennis F. A., Martin W. J., Verbonitz M. W. Cytotoxic T lymphocytes induced in mice by inactivated influenza virus vaccine. Nature. 1977 Sep 29;269(5627):418–419. doi: 10.1038/269418a0. [DOI] [PubMed] [Google Scholar]
  14. Ennis F. A., Martin W. J., Verbonitz M. W. Hemagglutinin-specific cytotoxic T-cell response during influenza infection. J Exp Med. 1977 Sep 1;146(3):893–898. doi: 10.1084/jem.146.3.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Floc'h F., Werner G. H. Heterotypic protective immune reactions in mice infected with distinct serotypes of human influenza virus. Ann Microbiol (Paris) 1978 May-Jun;129(4):509–524. [PubMed] [Google Scholar]
  16. Gething M., Koszinowski U., Waterfield M. Fusion of Sendai virus with the target cell membrane is required for T cell cytotoxicity. Nature. 1978 Aug 17;274(5672):689–691. doi: 10.1038/274689a0. [DOI] [PubMed] [Google Scholar]
  17. Helenius A., Fries E., Kartenbeck J. Reconstitution of Semliki forest virus membrane. J Cell Biol. 1977 Dec;75(3):866–880. doi: 10.1083/jcb.75.3.866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hoffmann M., Kappler J. W. The antigen specificity of thymus-derived helper cells. J Immunol. 1972 Jan;108(1):261–263. [PubMed] [Google Scholar]
  19. Huang R. T., Wahn K., Klenk H. D., Rott R. Association of the envelope glycoproteins of influenza virus with liposomes--a model study on viral envelope assembly. Virology. 1979 Aug;97(1):212–217. doi: 10.1016/0042-6822(79)90390-8. [DOI] [PubMed] [Google Scholar]
  20. Jackson D. C., Ada G. L., Hapel A. J., Dunlop M. B. Changes in the surface of virus-infected cells recognized by cytotoxic T cells. II. A requirement for glycoprotein synthesis in virus-infected target cells. Scand J Immunol. 1976;5(9):1021–1029. doi: 10.1111/j.1365-3083.1976.tb03054.x. [DOI] [PubMed] [Google Scholar]
  21. Kilbourne E. D. Influenza as a problem in immunology. J Immunol. 1978 May;120(5):1447–1452. [PubMed] [Google Scholar]
  22. Kindred B., Corley R. B. Specificity of helper T cells for different antigens. Eur J Immunol. 1978 Jan;8(1):67–71. doi: 10.1002/eji.1830080114. [DOI] [PubMed] [Google Scholar]
  23. Koszinowski U. H., Simon M. M. Generation of virus-specific cytotoxic T cells in vitro. I. Induction conditions of primary and secondary Sendai virus-specific cytotoxic T cells. Eur J Immunol. 1979 Sep;9(9):715–722. doi: 10.1002/eji.1830090910. [DOI] [PubMed] [Google Scholar]
  24. Koszinowski U., Gething M. J., Waterfield M. T-cell cytotoxicity in the absence of viral protein synthesis in target cells. Nature. 1977 May 12;267(5607):160–163. doi: 10.1038/267160a0. [DOI] [PubMed] [Google Scholar]
  25. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  26. Lohmeyer J., Talens L. T., Klenk H. D. Biosynthesis of the influenza virus envelope in abortive infection. J Gen Virol. 1979 Jan;42(1):73–88. doi: 10.1099/0022-1317-42-1-73. [DOI] [PubMed] [Google Scholar]
  27. MacDonald H. R. Energy metabolism and T-cell-mediated cytolysis. II. Selective inhibition of cytolysis by 2-deoxy-D-glucose. J Exp Med. 1977 Sep 1;146(3):710–719. doi: 10.1084/jem.146.3.710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Morein B., Barz D., Koszinowski U., Schirrmacher V. Integration of a virus membrane protein into the lipid bilayer of target cells as a prerequisite for immune cytolysis. Specific cytolysis after virosome-target cell fusion. J Exp Med. 1979 Dec 1;150(6):1383–1398. doi: 10.1084/jem.150.6.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nakamura K., Compans R. W. Effects of glucosamine, 2-deoxyglucose, and tunicamycin on glycosylation, sulfation, and assembly of influenza viral proteins. Virology. 1978 Feb;84(2):303–319. doi: 10.1016/0042-6822(78)90250-7. [DOI] [PubMed] [Google Scholar]
  30. Rosenthal A. S., Barcinski M. A., Blake J. T. Determinant selection is a macrophage dependent immune response gene function. Nature. 1977 May 12;267(5607):156–158. doi: 10.1038/267156a0. [DOI] [PubMed] [Google Scholar]
  31. Skehel J. J., Waterfield M. D. Studies on the primary structure of the influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 1975 Jan;72(1):93–97. doi: 10.1073/pnas.72.1.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sugamura K., Shimizu K., Zarling D. A., Bach F. H. Role of sendai virus fusion-glycoprotein in target cell susceptibility to cytotoxic T cells. Nature. 1977 Nov 17;270(5634):251–253. doi: 10.1038/270251a0. [DOI] [PubMed] [Google Scholar]
  33. Wrigley N. G. Electron microscopy of influenza virus. Br Med Bull. 1979 Jan;35(1):35–38. doi: 10.1093/oxfordjournals.bmb.a071539. [DOI] [PubMed] [Google Scholar]
  34. Yap K. L., Ada G. L. Cytotoxic T cells specific for influenza virus-infected target cells. Immunology. 1977 Feb;32(2):151–159. [PMC free article] [PubMed] [Google Scholar]
  35. Yap K. L., Ada G. L. The recovery of mice from influenza A virus infection: adoptive transfer of immunity with influenza virus-specific cytotoxic T lymphocytes recognizing a common virion antigen. Scand J Immunol. 1978;8(5):413–420. doi: 10.1111/j.1365-3083.1978.tb00536.x. [DOI] [PubMed] [Google Scholar]
  36. Yewdell J. W., Webster R. G., Gerhard W. U. Antigenic variation in three distinct determinants of an influenza type A haemagglutinin molecule. Nature. 1979 May 17;279(5710):246–248. doi: 10.1038/279246a0. [DOI] [PubMed] [Google Scholar]
  37. Zweerink H. J., Askonas B. A., Millican D., Courtneidge S. A., Skehel J. J. Cytotoxic T cells to type A influenza virus; viral hemagglutinin induces A-strain specificity while infected cells confer cross-reactive cytotoxicity. Eur J Immunol. 1977 Sep;7(9):630–635. doi: 10.1002/eji.1830070910. [DOI] [PubMed] [Google Scholar]
  38. Zweerink H. J., Courtneidge S. A., Skehel J. J., Crumpton M. J., Askonas B. A. Cytotoxic T cells kill influenza virus infected cells but do not distinguish between serologically distinct type A viruses. Nature. 1977 May 26;267(5609):354–356. doi: 10.1038/267354a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES